Improving natural product research translation: From source to clinical trial.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

High-performance Countercurrent Chromatography to Access Rhodiola rosea Influenza Virus Inhibiting Constituents.

In a cytopathic effect inhibition assay, a standardized Rhodiola rosea root and rhizome extract, also known as roseroot extract (SHR-5), exerted distinct anti-influenza A virus activity against HK/68 (H3N2) (IC50 of 2.8 µg/mL) without being cytotoxic. For fast and efficient isolation and identification of the extract's bioactive constituents, a high-performance countercurrent chromatographic separation method was developed. It resulted in a three-stage gradient elution program using a mobile phase solvent system composed of ethyl acetate/n-butanol/water (1 : 4 : 5 → 2 : 3 : 5 → 3 : 2 : 5) in the reversed-phase mode. The elaborated high-performance countercurrent chromatographic method allowed for fractionation of the complex roseroot extract in a single chromatographic step in a way that only one additional orthogonal isolation/purification step per fraction yielded 12 isolated constituents. They cover a broad polarity range and belong to different structural classes, namely, the phenylethanoid tyrosol and its glucoside salidroside, the cinnamyl alcohol glycosides rosavin, rosarin, and rosin as well as gallic acid, the cyanogenic glucoside lotaustralin, the monoterpene glucosides rosiridin and kenposide A, and the flavonoids tricin, tricin-5-O-ß-D-glucopyranoside, and rhodiosin. The most promising anti-influenza activities were determined for rhodiosin, tricin, and tricin-5-O-ß-D-glucopyranoside with IC50 values of 7.9, 13, and 15 µM, respectively. The herein established high-performance countercurrent chromatographic protocol enables fast and scalable access to major as well as minor roseroot constituents. This is of particular relevance for extract standardization, quality control, and further in-depth pharmacological investigations of the metabolites of this popular traditional herbal remedy.

Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia.

AIM: This study aimed to investigate the effect of adding ursodeoxycholic acid (UDCA) to phototherapy in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency and hyperbilirubinaemia. G6PD deficiency is a common cause of severe hyperbilirubinaemia in neonates. METHODS: This study was a triple blind, clinical trial study of 40 neonates with G6PD deficiency and hyperbilirubinaemia who admitted for phototherapy in hospitals affiliated to the University of Medical Sciences. The treatment group (n = 20) received UDCA 10 mg/kg (2 cc/kg) daily divided into 2 doses every 12 h. The control group (n = 20) received the same volume of placebo syrup. The drug and placebo treatments were continued until the bilirubin level dropped below 171 µmol/L. Both the control and treatment group received continuous phototherapy. Independent sample t-test, survival analysis and logrank test were used to statistically analyse the results. RESULTS: The mean total bilirubin level was 231.9 ± 18.8 µmol/L and 184.3 ± 18.6 µmol/L in the control and intervention group respectively, 24 h after drug administration and 209.7 ± 19.3 µmol/L and 157.4 ± 16.4 µmol/L, respectively, 48 h after intervention (P < 0.05). The median length of hospitalisation in the treatment group was approximately 1 day lower than the control group (logrank test P value: <0.001). CONCLUSION: The study showed that the addition of UDCA to phototherapy accelerates the reduction of total bilirubin level in neonates with G6PD deficiency and can reduce the duration of hospitalisation.

Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells.

A new coumarin, (-)-cis-(3'R,4'R)-4'-O-angeloylkhellactone-3'-O-ß-d-glucopyranoside (1) and two new chalcones, 3'-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2',4'-trihydroxychalcone (4) and (±)-4,2',4'-trihydroxy-3'-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3'-O-methylvaginol (3), (-)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6-9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1-9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress.

Green tea polyphenols require the mitochondrial iron transporter, mitoferrin, for lifespan extension in Drosophila melanogaster.

Green tea has been found to increase the lifespan of various experimental animal models including the fruit fly, Drosophila melanogaster. High in polyphenolic content, green tea has been shown to reduce oxidative stress in part by its ability to bind free iron, a micronutrient that is both essential for and toxic to all living organisms. Due to green tea's iron-binding properties, we questioned whether green tea acts to increase the lifespan of the fruit fly by modulating iron regulators, specifically, mitoferrin, a mitochondrial iron transporter, and transferrin, found in the hemolymph of flies. Publicly available hypomorph mutants for these iron regulators were utilized to investigate the effect of green tea on lifespan and fertility. We identified that green tea could not increase the lifespan of mitoferrin mutants but did rescue the reduced male fertility phenotype. The effect of green tea on transferrin mutant lifespan and fertility were comparable to w1118 flies, as observed in our previous studies, in which green tea increased male fly lifespan and reduced male fertility. Expression levels in both w1118 flies and mutant flies, supplemented with green tea, showed an upregulation of mitoferrin but not transferrin. Total body and mitochondrial iron levels were significantly reduced by green tea supplementation in w1118 and mitoferrin mutants but not transferrin mutant flies. Our results demonstrate that green tea may act to increase the lifespan of Drosophila in part by the regulation of mitoferrin and reduction of mitochondrial iron.

Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities.

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 µM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

Comparing Mobile-Based to Group-Based Education for Weight Reduction in a Developing Country: A Randomized Study.

Background: This study compared the impact of Short Message Service (SMS)-based education with traditional group-based education and the control group on body mass index, weight, and lifestyle in obese and overweight patients in a limited-resource country. It also compared the direct financial costs between the two intervention groups. Methods: In this controlled randomized educational study, 90 overweight or obese adults from four family physician clinics in Shiraz, Iran were randomly allocated to three training groups: SMS-based education, group-based education, and a control group. The participants' weight, body mass index (BMI), and waist circumference were measured at baseline, and the Physical Activity Scale questionnaire was completed. Group-based training was conducted in 1-hour weekly sessions. The SMS group received a text message each morning. The control group received routine care from a family physician. The intervention lasted 12 weeks. All participants were re-examined for the studied variables. Additionally, the direct costs were estimated, calculated, and compared. Results: The mean weight, BMI, and waist circumference changed significantly after 3 months compared to baseline in each group. The mean weight change differed significantly among the three groups (P-value=0.04), and the mean BMI changes were near significant (P-value=0.06). A post hoc comparison of changes in weight and BMI showed a significant difference between the control and SMS groups. SMS education incurred much lower costs for patients and healthcare services than group-based education. Conclusion: The study showed that SMS is an effective and cost-saving educational method for weight loss compared to group-based education, especially in developing countries.

COVID-19, stress and mental health: What students expect from academic institutions during a pandemic.

Objectives: To learn about the mental health of students, the tools they use to cope with stress, and their perceptions toward the assistance they receive from their academic institutions during the COVID-19 pandemic. Participants: 593 students from two University of California campuses. Methods: The link to an anonymous survey was included in a mass email that was sent to students. Results: 87% of students expressed that their mental health has been negatively impacted by the pandemic, especially in students who already had diminished levels of self-reported mental health. Students articulated the need for increased financial, academic, and mental health support and that they want to have a voice in discussions that will lead to decisions that would impact them. Conclusion: Students reported that the pandemic has negatively impacted their mental health and that they wanted academic institutions to include them in the decision-making processes that would contribute to their health.

Angelica keiskei Impacts the Lifespan and Healthspan of Drosophila melanogaster in a Sex and Strain-Dependent Manner.

Angelica keiskei is a perennial plant, belonging to the Apiaceae family and originating from Japan. This plant has been reported to act as a diuretic, analeptic, antidiabetic, hypertensive, tumor, galactagogue, and laxative. The mechanism of action of A. keiskei is not known, but previous studies have suggested that it may act as an antioxidant. In this work, we used Drosophila melanogaster to evaluate the impact of A. keiskei on lifespan and healthspan and its potential anti-aging mechanism by conducting multiple assays on three fly strains: w1118, chico, and JIV. We observed that the extract extended lifespan and improved healthspan in a sex- and strain-dependent manner. A. keiskei extended lifespan and improved reproductive fitness in female flies and either had no effect or decreased survival and physical performance in males. The extract protected against the superoxide generator paraquat in both sexes. These sex-specific effects suggest that A. keiskei may act through age-specific pathways such as the insulin and insulin-like growth factor signaling (IIS) pathways. Upon examination, we found that the increased survival of A. keiskei-fed females was dependent on the presence of the insulin receptor substrate chico, supporting the role of IIS in the action of A. keiskei.

Chemotherapy-induced toxicity is highly heritable in Drosophila melanogaster.

OBJECTIVES: Identification of the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. To develop D. melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high-throughput toxicity assays and prove that the interindividual variation in toxicity as measured by such assays is highly heritable. METHODS: We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose-dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed by a decrease in female fecundity. The chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride. RESULTS: We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose-dependent and a highly heritable manner. The following heritability estimates were found: carboplatin, 0.72; floxuridine, 0.52; gemcitabine hydrochloride, 0.72; methotrexate, 0.99; mitomycin C, 0.64; and topotecan hydrochloride, 0.63. CONCLUSION: The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component.

Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy.

The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53-/- MEFs) compared to their wild-type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2-/-, p53-/- MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-α phosphorylation and a decrease of 4E-BP1 phosphorylation, leading to increased binding of 4E-BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis.

Extension of Drosophila lifespan by Rosa damascena associated with an increased sensitivity to heat.

Rosa damascena, or Damask rose, is a rose hybrid commonly harvested for rose oil used in perfumery and for rose water used to flavor food. The petal extract of R. damascena was recently found to decrease Drosophila melanogaster mortality without impairing reproductive fitness or metabolic rate. Here, we report that R. damascena extended both mean and maximum lifespan of the fly. The extract also protected against oxidative stress in flies, predominantly in females. However, it did not alter mitochondrial respiration or content, superoxide production, or the major antioxidant defenses, superoxide dismutase and catalase. The extract increased survival in both sexes when exposed to reduced iron, though surprisingly, it sensitized both sexes to heat stress (survival at 37°C), and appeared to down-regulate the major heat shock protein HSP70 and the small mitochondrial heat shock protein HSP22, at 25°C and after heat shock (4 h at 37°C). We hypothesize that R. damascena extends lifespan by protecting against iron, which concomitantly leads to decreased HSP expression and compromising heat tolerance.

Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain.

Gallic acid is known as a potent antioxidant active compound of the edible and medicinal plant Peltiphyllum peltatum. The main objective of this study was to evaluate the neuroprotective effects of gallic acid against sodium fluoride induced oxidative stress in rat brain. Gallic acid (10 and 20 mg/kg) and vitamin C (10 mg/kg) were intraperitoneally administrated for 1 week prior to sodium fluoride intoxication. After the treatment period, brain tissues were collected and homogenized, and antioxidant parameters were measured in the homogenates. The level of thiobarbituric acid reactive substances in sodium fluoride intoxicated rats (42.04 ± 2.14 nmol MDA eq/g tissue, p < 0.01 vs. normal) increased compared to the normal rats (35.99 ± 1.08 nmol MDA eq/g tissue). Pretreatment with gallic acid at 20 mg/kg was exhibited significant reduction in the thiobarbituric acid reactive substances level (37.06 ± 1.4 nmol MDA eq/g tissue, p > 0.05 vs. normal). This increasing in thiobarbituric acid reactive substances level was accompanied with a decrease in the level of reduced glutathione (6.74 ± 0.28 µg/mg of protein, p < 0.001 vs. normal), superoxide dismutase (53.24 ± 1.62 U/mg of protein, p < 0.001 vs. normal) and catalase (70.73 ± 2.94 µmol/min/mg of protein p < 0.001 vs. normal) activities in sodium fluoride intoxicated rat. Gallic acid at 20 mg/kg was significantly modified the level of reduced glutathione (11.02 ± 0.53 µg/mg of protein, p < 0.05 vs normal) and catalase activity (89.22 ± 3.67 µmol/min/mg of protein, p > 0.05 vs. normal) in rat brain. However, gallic acid at 20 mg/kg was significantly more effective in retrieving superoxide dismutase (124.78 ± 5.7 U/mg of protein) activity than vitamin C (115.5 ± 4.97 U/mg of protein).

The impact of Rhodiola rosea on biomarkers of diabetes, inflammation, and microbiota in a leptin receptor-knockout mouse model.

Type 2 diabetes is the most prevalent endocrine disease in the world, and recently the gut microbiota have become a potential target for its management. Recent studies have illustrated that this disease may predispose individuals to certain microbiome compositions, and treatments like metformin have been shown to change gut microbiota and their associated metabolic pathways. However, given the limitations and side effects associated with pharmaceuticals currently being used for therapy of diabetes, there is a significant need for alternative treatments. In this study, we investigated the effects of a root extract from Rhodiola rosea in a Leptin receptor knockout (db/db) mouse model of type 2 diabetes. Our previous work showed that Rhodiola rosea had anti-inflammatory and gut microbiome-modulating properties, while extending lifespan in several animal models. In this study, treatment with Rhodiola rosea improved fasting blood glucose levels, altered the response to exogenous insulin, and decreased circulating lipopolysaccharide and hepatic C-reactive protein transcript levels. We hypothesize that these changes may in part reflect the modulation of the microbiota, resulting in improved gut barrier integrity and decreasing the translocation of inflammatory biomolecules into the bloodstream. These findings indicate that Rhodiola rosea is an attractive candidate for further research in the management of type 2 diabetes.

The Pattern of Cyclosporine Nephrotoxicity and Urinary Kidney Injury Molecule 1 in Allogenic Hematopoietic Stem Cell Transplant Patients.

OBJECTIVES: The typical immunosuppressive regimen of hematopoietic stem cell transplant includes cyclosporine. However, cyclosporine nephrotoxicity is a concern. We studied cyclosporine nephrotoxicity epidemiology in hematopoietic stem cell transplant patients and compared the pattern and urinary levels of the KIM-1 kidney injury molecule versus serum and urine creatinine levels. MATERIALS AND METHODS: The study covered 10 months at Namazi Hospital, Shiraz, Iran. All patients met the following criteria: > 15 years old, received allogenic hematopoietic stem cell transplant without history of acute or chronic kidney disease, and scheduled for at least 1 week of cyclosporine treatment. Urinary and serum levels of creatinine, urea, sodium, potassium, magnesium, and the KIM-1 kidney injury molecule were measured on days 0, 3, 5, 7, 10, and 14 of cyclosporine treatment. RESULTS: Of 42 patients, one-third developed cyclosporine nephrotoxicity (30.95%), and median onset time was 15 days. Hypokalemia and hypomagnesemia were reported in 76.2% and 53.4% of the cohort, respectively. None of the demographic, clinical, and paraclinical parameters was significantly associated with cyclosporine nephrotoxicity. Median duration of hospital stay for patients with cyclosporine nephrotoxicity (41 days) was significantly higher (P < .001) than those without nephrotoxicity (29 days). Area under the curve for receiver operating characteristic showed that accuracy of serum creatinine (0.267; 95% CI, 0.11-0.43) at day 0 of cyclosporine treatment was significantly lower (P = .017) than the accuracy of urine creatinine (0.477; 95% CI, 0.28-0.67) and urine levels of the KIM-1 kidney injury molecule (0.594; 95% CI, 0.41-0.78). CONCLUSIONS: Cyclosporine nephrotoxicity is a common adverse effect in the setting of hematopoietic stem cell transplant and occurs mostly within the first 2 weeks of cyclosporine treatment. Urine KIM-1 kidney injury molecule measurement had no overall superiority and no improved accuracy over serum or urine creatinine measurements for prediction or detection of cyclosporine nephrotoxicity.

Burnout Comparison between Clinical and Basic Sciences Faculty of a Medical School and Evaluation of Related Factors.

Objective: It has been shown that clinical practice may be a risk factor for job burnout. On the other hand, annual income may have a protective effect on job burnout. Clinical faculty in contrast to basic sciences faculty members have higher income but are involve in clinical practice. Comparison between these two groups can clarify which factors have greater influence on burnout. As a second aim for this study, reliability and validity of the Persian version of Maslach burnout inventory general survey (MBI-GS) were evaluated as well. Method : This cross-sectional study was conducted at Shiraz Medical School in Iran and a total of 241 faculty members were randomly selected and burnout was measured by the Persian version of the Maslach burnout inventory general survey (MBI-GS). Results: Comparison of burnout between the two groups indicated that clinical faculty showed significantly higher scores in the exhaustion dimension compared to the basic sciences faculty (p value = 0.017) but no significant differences were found between the two groups in other dimensions. Job satisfaction and income satisfaction were negatively correlated with exhaustion and cynicism dimensions, and job satisfaction was positively associated with professional efficacy (p value > 0.05). Internal consistency of the questionnaire was acceptable (α=0.77). Scaling success rate for discrimination and convergent validity were 100% except for convergent validity in the cynicism subscale. Correlation of all questions with their dimensions was equal to or more than 0.4 with the exception of item 13 in the cynicism subscale. Conclusion: Clinical faculty had higher burnout than basic sciences faculty especially in the exhaustion dimension. It has also been shown that income and job satisfaction are the most important factors which can predict professional burnout in medical faculty members. It is important for administrative and organizational decision makers to improve job engagement and decrease job abandonment. This study largely confirmed the 3-dimensional structure of the Persian version of MBI-GS.

Persian Version of the Yale Food Addiction Scale 2.0: Psychometric Analysis and Setting Cutoff Point for the Food Cravings Questionnaire-Trait-Reduced.

OBJECTIVE: The aims of this study were to evaluate the psychometric properties of Persian translation of the Yale Food Addiction Scale 2.0 (YFAS 2.0) as a widely accepted questionnaire for the first time and to establish a cut off score for Food Craving Questionnaire-Trait-reduced (FCQ-T-r). METHODS: In this cross-sectional study, 330 visitors of family physician clinics in Shiraz, a city located in south of Iran, were selected. The English version of YFAS 2.0 was translated into Persian and used in this study as well as the Persian version of FCQ-T-r. RESULTS: Confirmatory factor analysis of YFAS-2 confirmed one dimensional structure and factor loading in all eleven symptoms was above 0.4. Internal consistency for eleven symptoms was 0.813. Prevalence of food addiction in participants was 6.7% (22 participants). BMI and FCQ-T-r questionnaire score both were positively correlated with the number of food addiction symptoms but age was negatively correlated with the number of the symptoms. The ROC curve analysis showed the best suggested cut-off point for FCQ-T-r questionnaire to detect food addiction was 32.5. CONCLUSION: The present study confirmed validity and reliability of Persian version of YFAS-2. It is suggested that food addiction occurs in different level of food craving behavior in different food cultures or genetics.

Diet and Botanical Supplementation: Combination Therapy for Healthspan Improvement?

Healthspan science aims to add healthy, functional years to human life. Many different methods of improving healthspan have been investigated, chiefly focusing on just one aspect of an organism's health such as survival. Studies in Drosophila melanogaster have demonstrated that a reversal to a long-abandoned ancestral diet results in improved functional health, particularly at later ages. Meanwhile, pharmaceutical studies have demonstrated that botanical extracts have potent antiaging properties, capable of extending the mean lifespan of D. melanogaster by up to 25%, without a decrease in early fecundity. In this study, we combine these two different approaches to healthspan extension to examine whether a combination of such treatments results in a synergistic or antagonistic effect on Drosophila healthspan. One botanical extract, derived from Rhodiola rosea, mimicked the effects of the ancestral apple diet with better performance at later ages compared with the control. Another extract, derived from Rosa damascena, decreased age-specific survivorship when combined with the apple diet providing support for the "Poisoned Chalice" hypothesis that combinations of various supplements or diets can elicit adverse physiological responses. More experiments in model organisms should be completed researching the effects of combining healthspan-extending substances in various diet backgrounds.

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation.

Foreign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials.

Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.

The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.