Metabolic profiling in the hypothalamus of aged mice.

Metabolic abnormalities are tightly connected to the perturbation of normal brain functions, thereby causing multiple neurodegenerative diseases. The hypothalamus is the master unit that controls the whole-body energy homeostasis. Thus, altered metabolic activity in the hypothalamus could be a crucial clue to better understand the development of metabolic disorders during aging. The current study aimed to investigate the changes in hypothalamic metabolites according to the aging process using gas chromatography-mass spectrometry. We identified that multiple metabolites and neurotransmitters were effectively reduced in the hypothalamus of aged mice. In addition, we observed increased levels of genes linked to the production and utilization of monocarboxylates in the aged hypothalamus, indicating the initiation of metabolic activity to produce alternative nutrient sources. Lastly, we found a reduced number of astrocytes in the hypothalamus of aged mice, suggesting that reduced nutrient availability in the hypothalamus might be associated with the decreased activity of astrocytes during aging. Collectively, the present study suggests that the deterioration of metabolic activities in the hypothalamus might be a primary cause and/or outcome of metabolic diseases associated with the aging process.

Antioxidant and Anti-Melanogenesis Effects of Colloidal Gold Camellia sinensis L. Extracts.

Green tea extract derived from the leaves of Camellia sinensis L. (CS), is a representative beverage with antioxidant, anti-cancer, and anti-viral properties. CS extract is also used in cosmetics. Colloidal gold is generally a sol or colloidal suspension of gold nanoparticles in water. Colloidal gold green tea (CGCS), cultivated as a fertilizer using this colloidal gold solution, contains gold minerals and possesses anti-inflammatory, analgesic, and anti-tumor properties. However, the skin bioactivity of CGCS has not yet been investigated. In this study, we investigated the effect of the CGCS extract on skin whitening. CGCS extract contained high levels of phenols and flavonoids and displayed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity in a concentration-dependent manner. CGCS extract inhibited melanin synthesis and tyrosinase activity in B16F10 cells more effectively than the CS extract. Moreover, the CGCS extract decreased the expression levels of the melanogenesis-related proteins, tyrosinase, tyrosinase-related proteins (TRPs), and microphthalmia-associated transcription factor (MITF). In conclusion, our study showed that the CGCS extract inhibits the expression of tyrosinase, TRP-1, and TRP-2 via the downregulation of MITF, thereby inhibiting melanin synthesis. Therefore, CGCS can potentially be used as a skin-whitening ingredient in the cosmetic industry.

Deficiency of Tristetraprolin Triggers Hyperthermia through Enhancing Hypothalamic Inflammation.

Tristetraprolin (TTP), an RNA-binding protein, controls the stability of RNA by capturing AU-rich elements on their target genes. It has recently been identified that TTP serves as an anti-inflammatory protein by guiding the unstable mRNAs of pro-inflammatory proteins in multiple cells. However, it has not yet been investigated whether TTP affects the inflammatory responses in the hypothalamus. Since hypothalamic inflammation is tightly coupled to the disturbance of energy homeostasis, we designed the current study to investigate whether TTP regulates hypothalamic inflammation and thereby affects energy metabolism by utilizing TTP-deficient mice. We observed that deficiency of TTP led to enhanced hypothalamic inflammation via stimulation of a variety of pro-inflammatory genes. In addition, microglial activation occurred in the hypothalamus, which was accompanied by an enhanced inflammatory response. In line with these molecular and cellular observations, we finally confirmed that deficiency of TTP results in elevated core body temperature and energy expenditure. Taken together, our findings unmask novel roles of hypothalamic TTP on energy metabolism, which is linked to inflammatory responses in hypothalamic microglial cells.

Adiponectin Controls Nutrient Availability in Hypothalamic Astrocytes.

Adiponectin, an adipose tissue-derived hormone, plays integral roles in lipid and glucose metabolism in peripheral tissues, such as the skeletal muscle, adipose tissue, and liver. Moreover, it has also been shown to have an impact on metabolic processes in the central nervous system. Astrocytes comprise the most abundant cell type in the central nervous system and actively participate in metabolic processes between blood vessels and neurons. However, the ability of adiponectin to control nutrient metabolism in astrocytes has not yet been fully elucidated. In this study, we investigated the effects of adiponectin on multiple metabolic processes in hypothalamic astrocytes. Adiponectin enhanced glucose uptake, glycolytic processes and fatty acid oxidation in cultured primary hypothalamic astrocytes. In line with these findings, we also found that adiponectin treatment effectively enhanced synthesis and release of monocarboxylates. Overall, these data suggested that adiponectin triggers catabolic processes in astrocytes, thereby enhancing nutrient availability in the hypothalamus.

Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells.

Morin is a well-known flavonoid, and has been reported to have various properties, such as anti-cell death, antioxidant, and anti-inflammatory properties. Although studies on the biochemical and biological actions of morin have been reported, the melanin biosynthesis effects and molecular mechanisms are unknown. In this study, we first found that morin has the effect of enhancing melanin biosynthesis in B16F10 mouse melanoma cells, and analyzed the molecular mechanism. In this study, we examined the effects of morin on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and microphtalmia-associated transcription factor (MITF) in B16F10 mouse melanoma cells. Morin showed no cytotoxicity in the concentration range of 5-100 µM, and significantly increased the intracellular tyrosinase activity and melanin contents. In mechanism analysis, morin increased the protein expression of TRP-1, TRP-2, and MITF associated with melanogenesis. Furthermore, morin increased phosphorylated ERK and p38 at the early time, and decreased phosphorylated ERK after 12 h. The results suggest that morin enhances melanin synthesis through the MAPK signaling pathways in B16F10 mouse melanoma cells.

Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis.

OBJECTIVES: Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure. METHODS: Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure. RESULTS: Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent. CONCLUSIONS: For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies. REGISTRATION: Open Science Framework:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

RéSUMé: OBJECTIFS: Les recommandations existantes suggèrent d'envisager des corticostéroïdes pour le traitement complémentaire de la cellulite, mais cela est basé sur un seul essai avec une faible certitude des preuves. L'objectif était de déterminer si les anti-inflammatoires (anti-inflammatoires non stéroïdiens [AINS], corticostéroïdes) comme traitement d'appoint de la cellulite améliorent la réponse clinique et la guérison. MéTHODES: Revue systématique et méta-analyse comprenant des essais contrôlés randomisés de patients atteints de cellulite traités avec des antibiotiques, indépendamment de l'âge, du sexe, de la gravité et du contexte, et une intervention d'anti-inflammatoires (AINS ou corticostéroïdes) contre placebo ou sans intervention. Medline (PubMed), Embase (via Elsevier) et Cochrane CENTRAL ont été recherchés de la création au 1er août 2023. L'extraction des données a été effectuée indépendamment par paires. Le risque de biais a été évalué à l'aide de l'outil Cochrane sur le risque de biais 2. Les données ont été regroupées à l'aide d'un modèle à effets aléatoires. Les principaux résultats sont le temps de réponse clinique et de guérison. RéSULTATS: Cinq études (n = 331) ont été incluses, toutes des études adultes. Trois essais ont indiqué le délai de réponse clinique. Il y avait un avantage avec l'utilisation d'un AINS par voie orale comme traitement d'appoint au jour 3 (risque ratio 1,81, 95%CI 1,42 à 2,31, I2 = 0%). Il n'y avait pas de différence entre les groupes au jour 5 (rapport de risque 1,19, IC à 95% 0,62 à 2,26), bien que l'hétérogénéité était élevée (I2 = 96 %). La guérison clinique a été rapportée par trois essais, et il n'y avait aucune différence entre les groupes à tous les points de temps jusqu'à 22 jours. L'hétérogénéité statistique était modérée à faible. Les événements indésirables (N = 3 essais) étaient peu fréquents. CONCLUSIONS: Pour les patients atteints de cellulite, les meilleures données disponibles suggèrent que les anti-inflammatoires non stéroïdiens oraux (AINS) comme traitement d'appoint aux antibiotiques peuvent entraîner une amélioration de la réponse clinique précoce, bien que cela ne soit pas soutenu au-delà de quatre jours. Les données sont insuffisantes pour commenter le rôle des corticostéroïdes dans la réponse clinique. Ces résultats doivent être interprétés avec prudence en raison du petit nombre d'études incluses. ENREGISTREMENT: Cadre de la science ouverte:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Online Knowledge Translation Program Involving Video Games and University Student-Led Tutorials About Cannabis and Psychosis for Black Youth: Mixed Method Feasibility Study.

BACKGROUND: We have piloted a new online knowledge translation (KT) program created to educate youth about cannabis effects, which uniquely focuses on mental health risks for Black youth. Youth are generally unaware of the research linking underage usage and the risk of psychosis. Youth from some Black racialized communities in Ontario may be disproportionately affected and in need of this knowledge. OBJECTIVE: Because very little is known about the acceptability and feasibility of programs educating Black youth about cannabis and psychosis risk, we evaluated this KT program, which consists of tutorials facilitated by university students and video games. METHODS: This mixed methods pilot study evaluates the transfer of knowledge about cannabis and psychosis risk before and after the online KT program and, at the same time, explores participant satisfaction with the program and views about underage use. Eligible participants were youth 16-19 years of age of Black African or Caribbean descent. Trained undergraduate students from McMaster University administered a quiz (psychosis and cannabis test; PCT) to evaluate knowledge before and after the KT program. After playing the psychoeducational video games, participants attended two tutorial group sessions led by undergraduate students. The undergraduate students facilitated the online tutorials about cannabis and psychosis. The tutorials augmented the educational content embedded within the gameplay: participants discussed what they learned from the video games and their understanding of psychosis and the effects of cannabis. In addition, undergraduate students qualitatively analyzed the tutorial discussions for themes, and the prequiz and postquiz scores were analyzed for significant differences in scores. RESULTS: A total of 9 Black youth were recruited and completed this pilot study. The mean PCT scores were 5.67 (SD 1.7) and 7.78 (SD 1.8) before and after the KT program, respectively. There was a significant improvement in scores (P<.05) post-KT program. Thematic analysis of the facilitated tutorials revealed three major themes: video game satisfaction, marijuana and psychosis literacy, and help-seeking awareness. Overall, participants showed an increased awareness and understanding of the subject matter after the gameplay and tutorial intervention. CONCLUSIONS: When supplemented with tutorial sessions, the Back to Reality Series shows promise for addressing the gap in knowledge about cannabis and psychosis, and the results provide preliminary evidence that the games appeal to Black youth.