Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms.

BACKGROUND: Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION: Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN: A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout. MEASURES AND OUTCOMES: Sleep was evaluated by polysomnography and 5 validated questionnaires. Serum indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro, Caco-2 cells were stimulated with interferon-gamma, and the ability of cherry juice procyanidin to inhibit IDO which degrades tryptophan and stimulates inflammation was measured. The content of procyanidin B-2 and other major anthocyanins in cherry juice were determined. RESULTS: Eleven subjects were randomized; 3 with sleep apnea were excluded and referred. The 8 completers with insomnia increased sleep time by 84 minutes on polysomnography (P = 0.0182) and sleep efficiency increased on the Pittsburgh Sleep Quality Index (P = 0.03). Other questionnaires showed no significant differences. The serum kynurenine-to-tryptophan ratio decreased, as did the level of prostaglandin E2 (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO. CONCLUSIONS: Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation, and may be partially responsible for improvement in insomnia.

APOBEC3 inhibits DEAD-END function to regulate microRNA activity.

The RNA binding protein DEAD-END (DND1) is one of the few proteins known to regulate microRNA (miRNA) activity at the level of miRNA-mRNA interaction. DND1 blocks miRNA interaction with the 3'-untranslated region (3'-UTR) of specific mRNAs and restores protein expression. Previously, we showed that the DNA cytosine deaminase, APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide like 3), interacts with DND1. APOBEC3 has been primarily studied for its role in restricting and inactivating retroviruses and retroelements. In this report, we examine the significance of DND1-APOBEC3 interaction. We found that while human DND1 inhibits miRNA-mediated inhibition of P27, human APOBEC3G is able to counteract this repression and restore miRNA activity. APOBEC3G, by itself, does not affect the 3'-UTR of P27. We found that APOBEC3G also blocks DND1 function to restore miR-372 and miR-206 inhibition through the 3'-UTRs of LATS2 and CX43, respectively. In corollary experiments, we tested whether DND1 affects the viral restriction function or mutator activity of APOBEC3. We found that DND1 does not affect APOBEC3 inhibition of infectivity of exogenous retrovirus HIV (ΔVif) or retrotransposition of MusD. In addition, examination of Ter/Ter;Apobec3-/- mice, lead us to conclude that DND1 does not regulate the mutator activity of APOBEC3 in germ cells. In summary, our results show that APOBEC3 is able to modulate DND1 function to regulate miRNA mediated translational regulation in cells but DND1 does not affect known APOBEC3 function.

Knowledge, attitude, and practice of Nepalese residents in the prevention and control of COVID-19: A cross-sectional web-based survey.

Background: Coronavirus disease 2019 (COVID-19) has caused a global public health crisis. Preventive measures to tackle the deadly virus are influenced by people's knowledge, attitude, and practice (KAP) toward COVID-19. This study aimed to assess the level of knowledge, attitude, and practice toward COVID-19 among Nepalese residents in Nepal. Methodology: A web-based cross-sectional survey was conducted among 755 Nepalese residents across all seven provinces of Nepal. The questionnaire used to determine the KAP of the participants was derived from a previous study conducted in Nepal. Descriptive analysis was done to identify the distribution of socio-economic and demographic characteristics of participants. Factors associated with residents' KAP regarding COVID-19 were examined using Chi-square tests at the significance level of 0.05. Results: The mean age of the participants was 24.6 years. At the time of data collection, 8.2% of the participants had their families in isolation or quarantine center. In this study, 76.4%, 58.0%, and 63.6% of the participants had a good knowledge level, attitude level, and practice level respectively regarding COVID-19. Occupation and marital status were significantly associated with knowledge, attitude, and practice level. Age was significantly associated with knowledge and attitude level. Those participants who had their family members in quarantine were found to have a good level of preventive practice. The knowledge-attitude (rka = 0.184, p < 0.001), attitude-practice (rap = 0.125, p < 0.001) and knowledge-practice (rkp = 0.07, p < 0.05) were positively correlated in this study. Conclusion: This study showed satisfactory awareness regarding COVID-19 among Nepalese residents. Community-based health education programs should be promoted to develop a positive attitude toward healthy practices to tackle the COVID-19 pandemic or any future health crisis.

Cytotoxicity of juglone and thymoquinone against pancreatic cancer cells.

Juglone and thymoquinone are cytotoxic to pancreatic cancer cells. The aim of this study was to investigate, using an analysis of isobolograms, the type and degree of interactions between juglone and thymoquinone on MIA PaCa-2 pancreatic cancer cells. Cell viability was evaluated using the MTT assay. Cell death was determined by flow cytometry. The IC50 value for juglone and TQ in combination was found to be 24.75 µM, which was higher than juglone or TQ alone. Juglone alone killed Mia Paca-2 cells by ferroptosis. At concentrations where 10, 20 or 50% of cells were affected, there existed a moderate antagonistic relationship between juglone and TQ as indicated by the combination index (CI) value determined by the Compusyn software. At concentrations that affected 75% and 90% of cells, there were nearly an additive effect with CI value of 1.09249 and 0.92391, respectively. Moderate synergism was only seen at concentration where 95% of cells were affected, and the corresponding concentration of juglone and TQ at that combination was 40.90 µM and 511.19 µM, respectively.

An extract of Artemisia dracunculus L. stimulates insulin secretion from ß cells, activates AMPK and suppresses inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia dracunculus L. (Russian tarragon) is a perennial herb belonging to the family Compositae and has a history of medicinal use in humans, particularly for treatment of diabetes. AIM OF THE STUDY: In this study a defined plant extract from A. dracunculus L. (termed PMI-5011) is used to improve beta(ß) cells function and maintain ß cell number in pancreatic islets as an alternative drug approach for successful treatment of diabetes. MATERIALS AND METHODS: Mouse and human pancreatic beta cells were treated with defined plant extract of A. dracunculus L. (PMI-5011) to understand the mechanism(s) that influence beta cell function and ß cell number. RESULTS: We found that the PMI-5011 enhances insulin release from primary ß cells, isolated mouse and human islets and it maintains ß cell number. Insulin released by PMI-5011 is associated with the activation of AMP-activated protein kinase (AMPK), and protein kinase B (PKB). Furthermore, PMI-5011 suppresses LPS/INFγ-induced inflammation and inflammatory mediator(s) in macrophages. PMI-5011 inhibited Nitric oxide (NO) production and expression of inducible nitric oxide synthase (iNOS) at the protein level and also attenuated pro-inflammatory cytokine (IL-6) production in macrophages. CONCLUSION: PMI-5011 has potential therapeutic value for diabetes treatment via increasing insulin release from ß cells and decreases capacity of macrophages to combat inflammation.