Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Strictosamide alleviates acute lung injury via regulating T helper 17 cells, regulatory T cells, and gut microbiota.

BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Chronic social comparison elicits depression- and anxiety-like behaviors and alterations in brain-derived neurotrophic factor expression in male rats.

Social comparison is a fundamental human characteristic; however, long-term social comparison may induce psychological stress and can lead to depression and anxiety. Recent studies have shown that nonhuman primates compare themselves with others; however, no studies have investigated whether social comparisons exist among rodents. In the present study, we established a rat model of social comparison. This model was subsequently used to examine the effects of the differential environment of a partner on depression- and anxiety-like behaviors in male rats, as well as to assess the changes in serum, medial prefrontal cortex (mPFC), and dorsal hippocampus brain-derived neurotrophic factor (BDNF) levels induced by long-term social comparison. Compared to rats whose partners were exposed to the same environment, rats whose partners were exposed to two combined enriched environmental stimuli for 14 days showed significantly decreased social novelty preference and sucrose consumption. No anxiety-like behaviors were observed. Rats whose partners were exposed to one enriched environment for 31 days showed significantly increased immobility time in the forced swimming test, and significantly decreased time spent in the center area in the open-field test. Further, rats whose partners were exposed to one enriched environment for 31 days showed lower BDNF levels in the mPFC and dorsal hippocampus, but not following partner exposure for 14 days. These results suggest that social comparisons exist in rats and can induce psychosocial stress and other negative affect. This model will not only provide the possibility to reveal the neurobiological basis of the emotional impact of social comparison, but could also be used to confirm the conservative evolutionary characteristics of social comparison as a behavioral attribute.

Clinical factors affecting the long-term survival of breast cancer patients.

OBJECTIVE: The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. METHODS: Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. RESULTS: Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. CONCLUSIONS: Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

Cynanotophyllosides E-F, two minor pregnane glycosides from the roots of cultivated Cynanchum otophyllum.

Cynanotophyllosides E-F, two new minor pregnane glycosides were isolated from the antidepressant active fraction of cultivated Cynanchum otophyllum, and their structures were determined as 12-O-vanilloyl-deacetylmetaplexigenin 3-O-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-digitoxopyranoside, and 12-O-nicotinoyl-deacetylmetaplexigenin 3-O-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-oleandropyranosyl-(1→4)-ß-D-cymaropyranoside respectively, with the combination of spectroscopic and chemical analysis.

[Effects of Bupleurum chinense on the diversity of intestinal flora in depressed mice].

Bupleuri Radix, serving as the sovereign medicinal in many antidepressant compound preparations, has been proved effective in treating depression in mice, but its effect on the intestinal flora remains unclear. The present study aimed to investigate the effects of Bupleurum chinense(one of the original materials of Bupleuri Radix) on the behaviors and the diversity of intestinal flora of depressed mice. A depression mouse model was induced by repeated social defeat stress. Specifically, C57 BL/6 J male mice were exposed to the attack from the CD-1 mice. Then, C57 BL/6 J male mice were divided into a depression group and a B. chinense group, with normal saline and B. chinense administered(ig) respectively. Sucrose preference test and tail suspension test were conducted during and after the experiment respectively, to analyze the effects of B. chinense on the behaviors of the depressed mice. The feces were collected after the experiment. The V3-V4 16 S rDNA regions of intestinal flora of mice in each group were sequenced by Ion S5 TMXL for the analysis of the number of operational taxonomic units(OTUs), richness, alpha and beta diversity indexes, and differential phyla and genera. The results indicated that B. chinense could decrease depressive-like behaviors of mice, increase sucrose preference, and shorten the time of immobility in tail suspension test. After B. chinense intervention, the relative abundance of Firmicutes was significantly decreased, while that of Bacteroidetes was increased at the phylum level. At the genus level, the relative abundance of Lactobacillus and Lachnoclostridium decreased(P<0.05), while that of Bacteroides, Alistopes, etc. was elevated(P<0.05). The findings demonstrate that B. chinense can regulate the intestinal flora and improve the depressive-like behaviors of mice with depression.

Determination of nootkatone in rat plasma by LC-tandem mass spectrometry and its application in a pharmacokinetic study.

This study aimed to develop a rapid, sensitive, and specific LC-tandem mass spectrometry method for the determination of nootkatone in rat plasma. α-Cyperone was chosen as the internal standard (IS). The plasma was processed using a one-step acetonitrile protein precipitation method. Chromatographic separation of nootkatone was achieved on a Phenomenex Kinetex XB-C18 column (2.10 × 50 mm, 2.6 µm) at 35°C with a mobile phase consisting of acetonitrile and water under a gradient elution at a flow rate of 0.35 mL/min. An electrospray ionization source was applied and operated in positive ion and multiple reaction monitoring modes. Nootkatone and IS were quantified using the transitions of m/z 219.200 → 163.110 and m/z 219.200 → 111.000, respectively. The calibration curves were linear over the range of 10-2000 ng/mL (r = 0.9943). The lower limit of quantification was 10 ng/mL. The intra- and inter-day precision (relative standard deviation) ranged from 2.56% to 8.41%, with the accuracy values ranging from 98.9% to 99.17% for four different concentration levels. The matrix effect and extraction recovery were within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of nootkatone in rats after oral and intravenous administration at three dosages. The main pharmacokinetic parameters were calculated, showing low bioavailability of nootkatone.

A new indole alkaloid with HUVEC proliferation activities from Nauclea officinalis.

A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique.

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next-generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3-internal tandem duplication (FLT3-ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation . In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse-free survival (RFS), DNMT3A, FLT3-ITD, or RUNX1 mutation predicted a higher likelihood of remission-induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3-ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation-related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.

Genome-wide characterization and expression analysis of geranylgeranyl diphosphate synthase genes in cotton (Gossypium spp.) in plant development and abiotic stresses.

BACKGROUND: GGPP (geranylgeranyl diphosphate) is produced in the isoprenoid pathway and mediates the function of various plant metabolites, which is synthesized by GGPPS (GGPP synthases) in plants. GGPPS characterization has not been performed in any plant species except Arabidopsis thaliana. Here, we performed a complete computational and bioinformatics analysis of GGPPS and detected their transcription expression pattern in Gossypium hirsutum for the first time so that to explore their evolutionary relationship and potential functions. Finally, we unravelled evolutionary relationship, conserved sequence logos, gene duplication and potential involvement in plant development and abiotic stresses tolerance of GGPPS genes in G. hirsutum and other plant species. RESULTS: A total of 159 GGPPS genes from 18 plant species were identified and evolutionary analysis divided these GGPPS genes into five groups to indicate their divergence from a common ancestor. Further, GGPPS family genes were conserved during evolution and underwent segmental duplication. The identified 25 GhGGPPS genes showed diverse expression pattern particularly in ovule and fiber development indicating their vital and divers roles in the fiber development. Additionally, GhGGPPS genes exhibited wide range of responses when subjected to abiotic (heat, cold, NaCl and PEG) stresses and hormonal (BL, GA, IAA, SA and MeJA) treatments, indicating their potential roles in various biotic and abiotic stresses tolerance. CONCLUSIONS: The GGPPS genes are evolutionary conserved and might be involve in different developmental stages and stress response. Some potential key genes (e.g. GhGGPP4, GhGGPP9, and GhGGPP15) were suggested for further study and provided valuable source for cotton breeding to improve fiber quality and resistant to various stresses.

Effect of Alpina oxyphylla extract on streptozotocin-induced kidney injure via regulating TGF-ß1 and MyD88.

BACKGROUND: Abnormal renal metabolism is closely related to the development of chronic kidney disease. It is well known that renal inflammation plays an important role in the occurrence and development of tubulointerstitial damage in the renal tubules. The purpose of the experiment was to observe the bioactivity of Alpina oxyphylla extract (AOE) on renal injury in diabetic nephropathy (DN) rats induced by streptozotocin (STZ). METHODS: Thirty male Wistar rats were randomly divided into five group (n = 6): (1) intact control (non-diabetic, ND); (2) intact diabetic (STZ), (3) diabetic rats treated with gliclazide 5 mg/kg (STZ-gli), (4) diabetic rats treated with AOE 400 mg/kg (AOE 400), (5) diabetic rats treated with AOE 800 mg/kg (AOE 800). The diabetic nephropathy rat model was established by single intraperitoneal injected 50 mg/kg STZ. Fasting blood glucose (FBG) and body weight was observed at 1、3、6 weeks. After 6 weeks, the renal function parameters of five groups and 24 h urinary protein were detected. Expression of transforming growth factor-beta1 (TGF-ß1) and myeloid differentiation factor 88 (MyD88) were assessed by Western Blot. RESULTS: The STZ group showed hyperglycemia, proteinuria, renal function damage, and the levels of 24 h urinary protein, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and interleukin-6 (IL-6) in the STZ group increased significantly compared with the ND group. The expression of TGF-ß1 in STZ group was increase (p < 0.01), and the expression of MyD88 was significantly lower than in ND group (p < 0.05). The treatment of DN rats with AOE attenuated DN-associated in the serum biochemical index and the expression of TGF-ß1. CONCLUSIONS: AOE can effectively protect kidney tissues of diabetic nephropathy, and probably through regulating level of TGF-ß1/MyD88.

Memory Retrieval-Extinction Combined With Virtual Reality Reducing Drug Craving for Methamphetamine: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Relapse, often precipitated by drug-associated cues that evoke craving, is a key problem in the treatment of methamphetamine use disorder (MUD). Drug-associated memories play a major role in the maintenance of relapse. Extinction training is a common method for decreasing drug craving by suppressing drug-associated memories. However, the effects are often not permanent, which is evident in form of spontaneous recovery or renewal of cue-elicited responses. Based on memory reconsolidation theory, the retrieval-extinction (R-E) paradigm may be more effective in decreasing spontaneous recovery or renewal responses than extinction. After the original memory reactivated to a labile state, extinction will be introduced within the reconsolidation window, thereby updating drug-associated memories. However, there are still some controversial results, which suggest that the reactivation of drug-associated memories and the 10 min-6 h of limited time window are two main elements in the R-E protocol. Virtual reality (VR) is supposed to promote memory reactivation by providing vivid drug-related stimuli when compared with movies. OBJECTIVE: The aim of this study is to examine the effectiveness of R-E training combined with VR on reducing spontaneous recovery or renewal of cue-elicited responses, in comparison to extinction, R-E training provided outside the time window of 6 h and R-E training retrieved using videos, in methamphetamine abusers. METHODS: The study is a parallel matched controlled study including 95 participants with MUD. Participants will be randomly assigned to either a R-10 min-E group (methamphetamine-related cues retrieval in VR followed by extinction after 10 min) or a NR-10 min-E group (neutral cues retrieval in VR followed by extinction after 10 min) or a R-6 h-E group (methamphetamine-related cues retrieval in VR followed by extinction after 6 h) or a RV-10 min-E group (methamphetamine-related cues retrieval in videos followed by extinction after 10 min). Cue-evoked craving and reactivity will be assessed at pre-test and at 1 day, 1 week, 1 month, and 6-month post-tests. DISCUSSION: To our knowledge, this study will probably be the first study to examine the efficacy of R-E training combined with VR to reduce cue-evoked responses in people with MUD. This innovative non-pharmacological intervention targeting drug-associated memories may provide significant clinical implications for reducing relapse, providing the study confirms its efficacy. CLINICAL TRIAL REGISTRATION: The trial is registered with Chinese Clinical Trial Registry at 17 October 2018, number: ChiCTR1800018899, URL: http://www.chictr.org.cn/showproj.aspx?proj=30854.

Single­cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction.

Single­cell RNA sequencing (scRNA­seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA­seq. Clustering methods were used to separate leukemia cells into different sub­populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT­rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA­seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.

Preparation and mechanism research of Ni-Co supported catalyst on hydrogen production from coal pyrolysis.

The combustible gas produced by coal pyrolysis can be used as a clean fuel to reduce environmental pollution caused by coal combustion. In order to improve the efficiency of coal pyrolysis to prepare flammable gases, Ni-Co supported pyrolysis catalysts were prepared by equal volume impregnation method using the pyrolysis coke of different pyrolysis final temperatures as the carrier in this study. The effects of different pyrolysis final temperatures and different metal loadings on pyrolysis products were studied. The cracking mechanism of the catalysts was characterized by BET, XRD, XPS and SEM. The results show that: (1) the catalytic efficiency of pyrolysis coke catalyst is mainly related to the metal type and loading of the additive. (2) The optimum preparation conditions for the supported catalyst are: use pyrolysis coke with 750 °C final pyrolysis temperature as the carrier, the loading amount of Ni is 5%, and the loading amount of Co is 8%.

Psychophysiological and self-reported responses in individuals with methamphetamine use disorder exposed to emotional video stimuli.

Individuals with methamphetamine use disorder (MUD) exhibit irritability and compulsive emotional responses, yet the relevant study is scarce. The characteristic of their positive and negative emotional responses can provide effective targets for the clinical intervention. In this study, we compared the emotional responses of 60 participants with MUD and 30 healthy participants to visual stimuli. They watched four types of video to elicit anger, fear, amusement, and joy emotional responses. The self-report of emotional responses (i.e., arousal, valence, and proximity), skin conductance level, and startle response were measured. Comparing to the healthy controls, the methamphetamine group's subjective arousal level of fear is significantly lower (t = 3.763, p < .01); the skin conductance level of joy is significantly higher (t = 2.086, p < .05), and the level of anger is marginal significantly higher (t = 1.984, p = .05); the startle response level of anger (t = 2.069, p < .05) and joy (t = 2.406, p < .05) is significantly higher. The methamphetamine group exhibited an enhanced emotion response to anger and a decreased response to joy which may indicate the emotion dysregulation problem caused by drug. These results provide effective targets for clinical intervention in treating patients of MUD with emotion dysregulation problems.

Identification of the Features of Emotional Dysfunction in Female Individuals With Methamphetamine Use Disorder Measured by Musical Stimuli Modulated Startle Reflex.

Emotional dysregulation contributes to the development of substance use disorders (SUDs) and is highly associated with drug abuse and relapse. Music as a contextual auditory stimulus can effectively stimulate the reward circuitry, modulate memory associated with drug taking, and enhance emotional experiences during drug taking. However, the studies of the emotional responses to music in individuals with SUDs are scarce. Using startle reflex and self-reports, this study assessed the psychophysiological and cognitive emotional responses (i.e., valence, arousal and proximity) to happy, peaceful, and fearful music stimuli in 30 females with methamphetamine use disorder (MUD) and 30 healthy females. The results found that participants with MUD showed an inhibited startle response to fearful music compared to normal controls (t = 3.7, p < 0.01), and no significant differences were found in the startle responses to happy and peaceful music between the two groups. For the self-reported ratings, participants with MUD showed a decreased arousal in the response to fearful (t = 4.1, p < 0.01) and happy music (t = 3.8, p < 0.01), an increased valence in the response to fearful music (t = 4.4, p < 0.01), and a higher level of proximity in the response to fearful (t = 3.8, p < 0.01) and happy music (t = 2.2, p = 0.03). No significant differences were found in the rating of arousal to peaceful music, the valence to happy and peaceful music, as well as the proximity to peaceful music between the two groups. The females with MUD showed attenuated psychophysiological response and potentiated cognitive response (i.e., valence, arousal) to fearful music, as well as a high proximity to musical stimuli with high arousal regardless of its valence. These results have important implications for promoting the effectiveness of assessment and therapy selections for female MUD patients with impaired emotion regulation.

Measurement of pharmacokinetics and tissue distribution of three bioactive constituents from Zanthoxylum armatum DC in rat plasma and tissues through UFLC-MS/MS.

The compounds of N-Methylanhydrotetrahydroberberrubine A, dictamnine and eudesmin were the primary bioactive components in the roots of Zanthoxylum armatum DC (Z. armatum). To clarify the pharmacokinetics and distribution of these three compounds, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was employed to determine the contents of these three compounds in rat plasma and seven tissues. The separation was achieved on a Kinetex XB-C18 100A column (2.1 × 50 mm, 2.6 µm, Phenomenex). The optimized mobile phase system was set with 0.1‰ formic acid aqueous solution (A) and acetonitrile (containing 0.1‰ formic acid) (B) with a programmed elution of 0.00 to 0.50 min, 2% B; 0.51-4.00 min, 30%-60% B; and 4.01-5.00 min, 2% B. All analytes were measured with optimized multiple reaction monitoring (MRM) in the positive ion ESI mode. Berberine hydrochloride was selected as the internal standard (IS). The MS/MS transitions of N-Methylanhydrotetrahydroberberrubine A, dictamnine, eudesmin and IS were 339.9135.1, 200.1 → 129.1, 387.4 → 369.0 and 337.1 → 321.1, respectively. The lower limits quantification (LLOQ) of the three analytes was 0.5-20 ng/ml. The linear ranges were 0.5-400 ng/ml for N-Methylanhydrotetrahydroberberrubine A and dictamnine and 20-4000 ng/ml for eudesmin. The present analysis showed that the two alkaloids were quickly absorbed, with Tmax in 0.167-0.292 h, and eudesmin was absorbed in 2.5 h. Moreover, all compounds were found at high concentrations in the gastrointestinal track. These results are helpful for further investigation of the clinical application of Z. armatum.

Questionnaire-Based Maladaptive Decision-Coping Patterns Involved in Binge Eating Among 1013 College Students.

Binge Eating Disorder (BED), considered a public health problem because of its impact on psychiatric, physical, and social functioning, merits much attention given its elevation to an independent diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Similar with substance use disorders, some neuropsychological and personality constructs are potentially implicated in the onset and development of BED, in which poor decision-making has been suggested to facilitate overeating and BED. The objective of this study was to investigate the associations between decision-coping patterns, monetary decision-making, and binge-eating behavior in young adults. A sample of 1013 college students, equally divided into binge-eating and non-binge-eating groups according to the scores on the Binge Eating Scale (BES), were administered multiple measures of decision-making including the Melbourne Decision-Making Questionnaire (MDMQ), the Delay-discounting Test (DDT), and the Probability Discounting Test (PDT). Compared with the non-binge-eating group, the binge-eating group displayed elevated scores on maladaptive decision-making patterns including Procrastination, Buck-passing, and Hypervigilance. Logistic regression model revealed that only Procrastination positively predicted binge eating. These findings suggest that different dimensions of decision-making may be distinctly linked to binge eating among young adults, with Procrastination putatively identified as a risk trait in the development of overeating behavior, which might promote a better understanding of this disorder.