Screening of Potential Anti-Thrombotic Ingredients from Salvia miltiorrhiza in Zebrafish and by Molecular Docking.

BACKGROUND: Danshen (DS), the dry root of Salvia miltiorrhiza Bge., has been used in traditional Chinese medicine (TCM) for many years to promote blood circulation and to inhibit thrombosis. However, the active ingredients responsible for the anti-thrombotic effect and the underlying mechanisms are yet to be fully elucidated. METHODS: Molecular docking was used to predict the active ingredients in DS and their potential targets by calculating the scores of docking between DS ingredients and thrombosis-related proteins. Then, a chemical-induced zebrafish thrombosis model was applied to confirm their anti-thrombotic effects. RESULT: The molecular docking results indicated that compared to the control ligand, higher docking scores were observed for several compounds in DS, among which salvianolic acid B (SAB), lithospermic acid (LA), rosmarinic acid (MA), and luteolin-7-O-ß-d-glucoside (LG) could attenuate zebrafish caudal vein thrombosis and recover the decrease in heart red blood cells (RBCs) in a dose-dependent manner. CONCLUSIONS: Our study showed that it is possible to screen the potential active components in natural products by combining the molecular docking method and zebrafish in vivo model.

Theoretical exploring of potential mechanisms of antithrombotic ingredients in danshen-chishao herb-pair by network pharmacological study, molecular docking and zebrafish models.

BACKGROUND: Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. METHODS: The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. RESULTS: DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 µg/mL. The co-administration of PF and SAA at 25 µg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein-protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. CONCLUSION: This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.

Characteristics of Adolescents with and without a Family History of Substance Use Disorder from a Minority Cohort.

Family history (FH+) of substance use disorder (SUD) is an established risk factor for offspring SUD. The extent to which offspring psychological traits or the family environment, each of which may be relevant to familial transmission of SUD risk, vary by FH+ in socioeconomically disadvantaged populations is less clear. We compared the family/social environmental and psychological characteristics of 73 FH+ and 69 FH- youth ages 12-16, from a study of parental criminal justice system involvement in a primarily low-income, minority urban population. A latent profile analysis (LPA) empirically identified groups of subjects with similar psychological characteristics, which were then compared by FH+. FH+ youths were found to have greater mean household size, greater parental psychological aggression, and a higher mean number of adverse childhood experiences, even without considering parental SUD. FH+ individuals had lower report card grades according to parental report and were more likely to have a history of externalizing disorders than FH- individuals. However, FH+ was not significantly associated with many psychological characteristics or with the class membership from the LPA. In conclusion, among a population of low-income, minority urban youth, FH+ was associated with differences in the family environment and only subtle differences in individual psychological characteristics.

Comparative study on main compounds and hypoglycemic effects of dispensing granules of Coptidis Rhizoma and Scutellaria-Coptis herb couple with traditional decoction.

BACKGROUND: The clinical applications of dispensing granules (DG) have increased dramatically. However, it is controversial whether the DG has the same quality and efficacy compared with traditional decoction (TD). In this study, the contents of main compounds, hypoglycemic effects, and potential mechanism of Coptidis Rhizoma (CR) and Scutellaria-coptis (SC), constituted of a 1:1 mixture of CR and Scutellariae Radix (SR), in the forms of TD and DG were compared. METHODS: The quantitative analysis was performed on an UPLC-PDA method. The 6-weeks-old male db/db mice were used as Type 2 Diabetes Mellitus (T2DM) mouse modle to investigate the antidiabetic effects of CR and SC in TD form (CR TD and SC TD), as well as CR and SC in DG form (CR DG and SC DG). RESULTS: The total content of five alkaloids in CR TD ranged from 71.00 to 78.62 mg, whereas in CR DG it ranged from 38.77 to 53.68 mg in CR DG per 1 g of decoction pieces. Compared to CR TD, CR DG exhibited a 36% reduction on average. For SC samples, the precipitation occurred in the processing of TD but not in the DG, and the relative ratio of alkaloids to flavonoids was determined to be 1:1 in TD and 1:2 in DG. Furthermore, the animal experiments showed that the CR DG (equivalent to 3 g decoction pieces/kg) had almost the same hypoglycemic effect as CR TD when they were administered for 6 weeks. Compared with SC DG (equivalent to 6 g decoction pieces/kg), SC TD showed a better trend in ameliorating T2DM via ameliorating pancreatic structure and function, and activating Akt/AMPK/GLUT4 signaling pathways. CONCLUSION: This study indicated that the contents of main compounds were generally higher in CR TD than CR DG originated from the same raw materials. Additionally, changes in the contents of the primary components validated that the compound interactions are exclusive to SC TD during co-decoction, rather than SC DG. The disparate prossing of SC DG and SC TD caused differences both in chemical composition and hypoglycemic effect, suggesting that the substitutability of DG and TD requires further research.

Racial and ethnic disparities in insufficient sleep among US in infants and preschoolers.

OBJECTIVE: To examine racial and ethnic disparities and associated factors of insufficient sleep among children from infancy to preschool-aged. METHODS: We analyzed parent-reported data on US children ages 4 months-5 years (n = 13,975) from the 2018 and 2019 National Survey of Children's Health. Children who slept less than the age-specific minimum hours recommended by the American Academy of Sleep Medicine were classified as having insufficient sleep. Logistic regression was used to estimate unadjusted and adjusted odds ratios (AOR). RESULTS: An estimated 34.3% of children from infancy to preschool-aged experienced insufficient sleep. Socioeconomic factors (poverty [AOR] = 1.5, parents' education level [AORs] from 1.3 to 1.5); parent-child interaction variables (AORs from 1.4 to 1.6); breast feeding status (AOR = 1.5); family structure (AORs from 1.5 to 4.4); and weeknight bedtime regularity (AORs from 1.3 to 3.0) were significantly associated with having insufficient sleep. Non-Hispanic Black (OR = 3.2) and Hispanic children (OR = 1.6) had significantly higher odds of insufficient sleep compared to non-Hispanic White children. Racial and ethnic disparities in insufficient sleep between non-Hispanic White children and Hispanic children were largely attenuated by adjusting for social economic factors. However, the difference in insufficient sleep between non-Hispanic Black and non-Hispanic White children remains (AOR = 1.6) after adjusting socioeconomic and other factors. CONCLUSIONS: More than one-third of the sample reported insufficient sleep. After adjusting for socio-demographic variables, racial disparities in insufficient sleep decreased but persistent disparities existed. Further research is warranted to examine other factors and develop interventions to address multilevel factors and improve sleep health among racial and ethnic minority group children.

White matter integrity and functional connectivity in adolescents with a parental history of substance use disorder.

A family history (FH+) of substance use disorder (SUD) increases an adolescent's risk for substance use initiation and progression. Greater impulsivity and reward seeking behavior is known to be associated with such risk. At the neurological level, dysfunction of cortico-striatal and cortico-limbic pathways have been proposed as contributors to the increased SUD risk in adolescents with FH+. In addition, disadvantaged environments have been associated with atypical brain connectivity and higher SUD risk. However, it remains unclear if this increased risk is manifested in structural and functional brain abnormalities prior to regular drug use. To examine this, we employed complementary imaging of structural and functional connectivity of 60 FH+ and 55 FH- minority adolescents, all from families with low socio-economic status. We acquired diffusion tensor-imaging (DTI) and resting state fMRI data across the whole brain. Structural connectivity was examined by measuring fractional anisotropy (FA) using DTI, to indicate integrity of the white matter tracts. Functional connectivity within and between resting state networks was assessed by the correlation of blood-oxygen-level-dependent (BOLD) signal between intra and inter-network nodes. Psychological measures of impulsivity and reward seeking were also obtained with standardized measures, the BIS-11 and the BIS/BAS, and their association with FA and functional connectivity was evaluated. We found no differences in white matter integrity between the groups. Compared to FH-, FH + adolescents showed significantly greater functional connectivity between posterior regions of the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN). While psychological measures of reward seeking behavior did not differ between the FH+ and FH- groups, impulsivity, assessed by the BIS-11, was significantly higher for FH+. However, we did not find significant differences between the FH+ and FH- groups when comparing associations of BIS-11 scores and white matter integrity or functional connectivity measures. The stronger inter-network functional connectivity between the DMN and FPN in FH + adolescents suggests that transmitted risk for SUD may be related to large-scale brain dynamics. The lack of structural differences support the importance of early prevention efforts for FH + adolescents, before initiation of drug use, allowing for healthy brain development.

Mental Health of High-Risk Urban Youth: The Housing Subsidies Paradox.

Housing subsidies, including public housing and Section 8 vouchers, are key components of the social safety net, intended to promote family and child welfare. Studies evaluating the impact of housing subsidies on child and adolescent mental health, however, are generally inconclusive. This may reflect variation in the influence by type of subsidies to income, improved physical environment, increased access to resources, and improved perception of neighborhood safety. Further, most prior research focused on housing subsidies failed to simultaneously formally assess child psychopathology. In the present study, we examine, among adolescents (ages 9-17) from a low-income, urban minority area, the association of housing with psychiatric symptoms and disorders, as well as with their social functioning. The data were obtained from the Stress & Justice Study (S&J) baseline survey, an investigation designed to examine impact of parental criminal justice system involvement (CJSI) on their children's mental health. Housing type during the past year was categorized from parental report as public housing, section 8, both, or neither. Child mental health was assessed with the Diagnostic Interview Schedule for Children (DISC). Additionally, family resources and physical quality of the housing environment by housing type was assessed, and we tested whether these dimensions mediated associations of housing type with the adolescent's current mental health outcomes. We found that while internalizing and externalizing disorders and impairment were attenuated by individual characteristics (e.g., SES, CJSI), internalizing and externalizing symptom counts were significantly more prevalent among children in subsidized housing, compared to those in non-subsidized housing, after controlling for individual characteristics. These findings have the potential to inform whether, and through which mechanisms, housing subsidies are associated with adolescent mental health.

Gut Microbiota Changes and Their Relationship with Inflammation in Patients with Acute and Chronic Insomnia.

PURPOSE: The major purpose of this study was to detect the changes in gut microbiota composition and inflammatory cytokines production associated with acute and chronic insomnia. This study also evaluated the relationship between gut microbiota changes and increased inflammatory cytokines in insomnia patients. PATIENTS AND METHODS: Outpatients with acute and chronic insomnia (aged 26-55 years; n=20 and 38, respectively) and age/gender-matched healthy controls (n=38) were recruited from a southern China region. Participants' gut microbiome, plasma cytokines, and self-reported sleep quality and psychopathological symptoms were measured. RESULTS: The gut microbiomes of insomnia patients compared with healthy controls were characterized by lower microbial richness and diversity, depletion of anaerobes, and short-chain fatty acid (SCFA)-producing bacteria, and an expansion of potential pathobionts. Lachnospira and Bacteroides were signature bacteria for distinguishing acute insomnia patients from healthy controls, while Faecalibacterium and Blautia were signature bacteria for distinguishing chronic insomnia patients from healthy controls. Acute/chronic insomnia-related signature bacteria also showed correlations with these patients' self-reported sleep quality and plasma IL-1ß. CONCLUSION: These findings suggest that insomnia symptomology, gut microbiota, and inflammation may be interrelated in complex ways. Gut microbiota may serve as an important indicator for auxiliary diagnosis of insomnia and provide possible new therapeutic targets in the field of sleep disorders.

Depressive symptoms between parent and adolescent survivors: A longitudinal actor-partner interdependence model.

BACKGROUND: The association between parent-child depression following disasters has been well documented. However, longitudinal studies of posttraumatic depression using parent-child dyadic are scarce. This study aimed to investigate inter-related effects between parent and child depression, as well as predictors of depressive symptoms, in a large sample of Wenchuan earthquake survivors. METHODS: Data are from the Wenchuan Earthquake Adolescent Health Cohort (WEAHC) Study that included 685 parent-child dyads exposed to the earthquake. Depression was assessed with the Self-Rating Depression Scale (for parents) and Depression Self-Rating Scale for Children, at 12 (T12m) and 18 months (T18m) post-earthquake. Longitudinal actor-partner interdependence models (APIMs) were employed to examine depression within dyads. Predictors of depressive symptoms were assessed by the cart algorithm throughout the 6-month follow-up. RESULTS: Adjusting for earthquake exposure and previous depressive symptoms, parents' depression at 12 months predicted children's depressive symptoms at 18 months, and vice versa (ß = 0.14 for parents and ß = 0.12 for children). Psychomotor retardation in parents, and dysphoria/social isolation and positive affect in children were identified as crucial screening indicators identifying parents and children at increased risk for depression. CONCLUSION: A bidirectional association was found between parent and child depression following a mass disaster. Both parent and child depression status should be examined when implementing interventions to identify and treat depression in earthquake survivors.

Neuroprotective effects of hydrogen sulfide and the underlying signaling pathways.

Hydrogen sulfide (H2S) is an endogenously produced gas that represents a novel third gaseous signaling molecule, neurotransmitter and cytoprotectant. Cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfur transferase with cysteine aminotransferase (3-MST/CAT) and 3-mercaptopyruvate sulfur transferase with d-amino acid oxidase (3-MST/DAO) pathways are involved in the generation of endogenous H2S despite the ubiquitous or restricted distribution of those enzymes. CBS, 3-MST/CAT and 3-MST/DAO can be found in the brain, while CSE is widely located in other organs. There also exist up-taking or recycling and scavenging mechanisms in H2S metabolism to maintain its persistence for physiological function. In recent years, investigating the role that H2S plays in the central nervous system and cardiovascular system has always been a hotspot. To date, effects of H2S are at least partially verified in multiple animal models or neuron cell lines of Alzheimer's disease, Parkinson's disease, cerebral ischemia, major depression disorders and febrile seizure, although subsequent studies are still badly needed. This article presents an overview of current knowledge of H2S focusing on its neuroprotective effects and corresponding signaling pathways, together with connections to potential therapeutic strategies in the clinic.