Gynostemma pentaphyllum Makino extract induces hair growth and exhibits an anti-graying effect via multiple mechanisms.

BACKGROUND: In traditional Asian medicine, Gynostemma pentaphyllum Makino leaf extract (Gp) is used to treat aging, metabolic syndrome, diabetes, and neurodegenerative diseases. Hair loss and hair-graying are common phenomena that haunt everyone. However, whether Gp activities on inhibition of hair loss and getting gray have been rarely studied. AIM: Study the Gp activity and mechanism by in vivo and in vitro experiments to explore its application on hair health. METHODS: In the present study, we determined the effects of Gp on the expression of hair growth-related genes and proliferation of human dermal papilla cells (hDPCs). Furthermore, Gp was topically applied to the hair-shaved skin of male C57BL/6 mice, and the histological profile of the skin was studied. Because emotional stress may lead to melanocyte disappearance, norepinephrine-exposed mice B16 melanocytes were treated with Gp to elucidate the anti-hair graying capacity of Gp in response to this stress type. RESULTS: Gp stimulated the proliferation of hDPCs and the Wnt signaling pathways associated with hair growth; furthermore, the expression of the hair loss-related gene transforming growth factor-ß1 was suppressed. Gp treatment significantly increased the size of hair follicles in the treated mice and stimulated them. Moreover, Gp not only increased melanin synthesis but also tyrosinase activity in B16 cells. Quantitative real-time polymerase chain reaction revealed that Gp increased melanin synthesis by increasing the expression of tyrosine-related protein-1, tyrosine-related protein-2, tyrosinase, and microphthalmia-associated transcription factor. CONCLUSION: Our study provides preclinical evidence regarding the potential of Gp as a promising hair growth and anti-graying agent.

Integrated network pharmacology and metabolomics to investigate the effects and possible mechanisms of Dehydroevodiamine against ethanol-induced gastric ulcers.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetradium ruticarpum (A.Juss.) T.G.Hartley, a traditional Chinese medicine with thousands of years of medicinal history, has been employed to address issues such as indigestion, abdominal pain, and vomiting. Dehydroevodiamine (DHE) is a quinazoline alkaloid extracted from traditional Chinese medicine Tetradium ruticarpum (A.Juss.) T.G.Hartley. Previous studies have shown that DHE has anti-inflammatory, analgesic, and antioxidant activities. However, it is still unclear whether DHE has an effect on ethanol-induced gastric ulcers. AIM OF THE STUDY: The objective of this study is to investigate the therapeutic efficacy and underlying mechanisms of action of DHE on ethanol-induced gastric ulcers using network pharmacology and metabolomics strategies. METHODS: In this study, we used ethanol-induced rats as a model to assess the efficacy of DHE by biochemical indicator assays and pathological tissue detection. The integration of network pharmacology and metabolomics was used to explore possible mechanisms and was validated by western blot experiments. Finally, molecular docking was used to analyze the binding energy between DHE and the targets of PIK3CG and PLA2G2A. RESULTS: DHE was able to reverse ethanol-induced abnormalities in biochemical indicators and improve pathological tissue. Network pharmacology results indicated that DHE may be involved in the regulation of gastric ulcers by modulating 79 targets, and metabolomics results showed that a total of 13 metabolites were changed before and after DHE administration. Integrating network pharmacology and metabolomics, PIK3CG and PLA2G2A were identified as possible targets to exert therapeutic effects. In addition, the MAPKs pathway may also be involved in the regulation of ethanol-induced gastric ulcers. Finally, molecular docking results showed that DHE had low binding energies with both PIK3CG and PLA2G2A. CONCLUSIONS: These findings suggest that DHE was able to exert a protective effect against ethanol-induced gastric ulcers by modulating multiple metabolites with multiple targets. This study provides a valuable reference for the development of antiulcer drugs.

Effect of Repeated Application of Flos Daturae on Sedative and Hypnotic in Mice.

Insomnia is one of the most common sleep-related diseases. In traditional Chinese medicine, Flos daturae has been used as a traditional herbal totreatment of sizens of diseases. The research objective was to investigate the sedative and hypnotic effects of Flos Daturae. Kunming mice were divided into control group, Estazolam (positive drug, 0.0005 g/kg) group and Flos Daturae groups (0.01, 0.02, 0.04g/kg) with random, ig once a day for 7 days. The central sedative effect of flos Daturae on the spontaneous activity of mice was observed using the locomotive activity test, and the hypnotic effect of Flos Daturae was observed in mice using the direct sleep test and the sleep latency with synergistic supra-and sub-threshold doses of pentobarbital sodium. Flos Daturae (0.04g/kg) significantly inhibited mice locomotive activity (P<0.05) and had no direct sleeping effect (P>0.05), increased the number rate of sleep (P<0.05), and significantly shortening sleep latency (P<0.05), enhanced pentobarbital sodium-induced sleep. Flos Daturae possesses have sedative-hypnotic properties.

Enhanced AMPAR-dependent synaptic transmission by S-nitrosylation in the vmPFC contributes to chronic inflammatory pain-induced persistent anxiety in mice.

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg-1·d-1, for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment.

Mechanism of Wuzhuyu decoction on alcohol-induced gastric ulcers using integrated network analysis and metabolomics.

Background: Gastric ulcers (GUs) are prevalent digestive disorders worldwide. Wuzhuyu Decoction (WZYT) is a traditional Chinese medicine that has been employed for centuries to alleviate digestive ailments like indigestion and vomiting. This study aims to explore the potential effects and underlying mechanisms of WZYT on alcohol induced gastric ulcer treatment. Methods: We employed macroscopic assessment to evaluate the gastric ulcer index (UI), while the enzyme-linked immunosorbent assay (ELISA) was utilized for detecting biochemical indicators. Pathological tissue analysis involved hematoxylin-eosin (H&E) staining and Periodic Acid-Schiff (PAS) staining to assess gastric tissue damage. Additionally, the integration of network analysis and metabolomics facilitated the prediction of potential targets. Validation was conducted using Western blotting. Results: The research revealed that WZYT treatment significantly reduced the gastric ulcer index (UI) and regulation of alcohol-induced biochemical indicators levels. Additionally, improvements were observed in pathological tissue. Network analysis results indicated that 62 compounds contained in WZYT modulate alcohol-induced gastric ulcers by regulating 183 genes. The serum metabolomics indicated significant changes in the content of 19 metabolites after WZYT treatment. Two pivotal targets, heme oxygenase 1 (HMOX1) and albumin (ALB), are believed to assume a significant role in the treatment of gastric ulcers by the construction of "compounds-target-metabolite" networks. Western blot analysis confirmed that WZYT has the capacity to elevate the expression of HMOX1 and ALB targets. Conclusion: The integration of network analysis and metabolomics provides a scientific basis to propel the clinical use of WZYT for GUs. Our study provides a theoretical basis for the use of Wuzhuyu decoction in the treatment of gastric ulcers.

[Quantitative proteomics reveals the abnormal liver metabolism-relieving effect of Anemarrhenae rhizoma in type 2 diabetes mellitus rats].

Type 2 diabetes mellitus (T2DM) is a global metabolic disease with potentially life- threatening complications. Liver metabolism plays a vital role in the occurrence and development of diabetes mellitus. It has been reported that the Chinese medicinal Anemarrhenae rhizoma (AR) can relieve insulin resistance and diabetes mellitus. However, the effect on abnormal liver metabolism in diabetes mellitus is still unclear. Therefore, we extracted liver proteins of T2DM rats induced by high-fat diet (HFD) and streptozotocin (STZ), T2DM rats treated with AR extract (ARE), obesity rats (fed with HFD), and normal control rats (fed with normal diet). Then, through tandem mass tag (TMT) labeling combined with mass spectrometry (MS), we obtained the quantitative proteomic data. Bioinformatics software was used for hierarchical cluster analysis and principal component analysis of the data in each group. The volcano map for differentially expressed proteins (P < 0.05, fold change > 1.5) was plotted. It was found that the treatment group was closer to the normal control group, indicating that the quantitative proteomic data of liver tissue can reflect the therapeutic effect of ARE on T2DM rats. Key protein clusters closely related to the treatment of ARE were screened out. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the protein clusters were analyzed by David, and the result showed that AR's alleviation of abnormal fatty acid metabolism in livers of T2DM rats may be related to the regulation of the expression of key proteins Ndufa6 and Prkar2b.

Exploring the Roles of Dispositional Mindfulness and Cognitive Reappraisal in the Relationship Between Neuroticism and Depression Among Postgraduate Students in China.

Objectives: Previous studies revealed a positive association between neuroticism and depression. This study further extended the previous findings by exploring the psychological processes underlying this association among Chinese postgraduates. Guided by theoretical models and empirical research, we proposed a multiple mediation and moderated mediation model to investigate the roles of dispositional mindfulness and cognitive reappraisal in the relationship between neuroticism and depression. Methods: Using the NEO Five-Factor Inventory, Beck Depression Inventory, Mindfulness Attention Awareness Scale, and Emotion Regulation Questionnaire, 1103 first-year postgraduates at a comprehensive university in China were surveyed. Path analysis was adopted to test the models. Results: The results showed that dispositional mindfulness mediated the association between neuroticism and depression. Further, this mediating effect was moderated by cognitive reappraisal, with this effect being stronger in individuals with low engagement in cognitive reappraisal. Conclusion: The results support interrelations among neuroticism, depression, dispositional mindfulness, and cognitive reappraisal as moderated mediation rather than multiple mediation. The results enhance our understanding of psychological mechanisms between neuroticism and depression and provide suggestions for interventions to prevent or reduce depression in highly neurotic postgraduates.

Competitive CatSper Activators of Progesterone from Rhynchosia volubilis.

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A - E (1:  - 5: ), a new natural product, 5'-O-methylphaseolinisoflavan (6: ) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7:  - 18: ). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1: ) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Impact of rhizosphere microorganisms on arsenic (As) transformation and accumulation in a traditional Chinese medical plant.

Panax notoginseng is an important traditional medicinal plant, but the commercial value is threatened by root-rot disease caused by rhizosphere microbes and a potential health risk caused by plant arsenic (As) accumulation. Whether rhizospheric microbes isolated from P. notoginseng rhizosphere soil could impact As uptake and transport into P. notoginseng is not yet known. Among the three root-rot disease-causing pathogens Fusarium flocciferum (PG 1), Fusarium oxysporum (PG 2), and Fusarium solani (PG 3) and one root-rot disease biocontrol fungus Trichoderma koningiopsis (FC 1) and five biocontrol-exerting bacterial species Bacillus siamensis (BC 1), Delftia acidovorans (BC 2), Brevibacillus formosus (BC 3), Mortierella alpine (BC 4), and Bacillus subtilis (BC 5), one As-resistant pathogen and four biocontrol microorganisms with As-resistant ability were identified. The As-transforming ability of the identified fungi and bacteria was ranked in the order of FC 1 > PG 1 and BC 2 > BC 3 > BC 1, respectively. Then, the As-resistant biocontrol and pathogenic microbes were initiated to colonize the rhizosphere of 1-year-old P. notoginseng seedlings growing in artificially As(V)-contaminated soil to evaluate the impact of microbe inoculation on P. notoginseng As uptake and transport capacity. Concentration of As in P. notoginseng tissues decreased in the order of the sequence stem > root > leaf. Compared to treatment without colonization by microorganism, inoculation with microorganisms increased As root uptake efficiency and root As concentration, especially under treatment of inoculation by BC 2 and PG 1 + BC 2. As transport efficiency from root to stem decreased by inoculation with microorganism, especially under treatment with inoculation of BC 2 and PG 1 + BC 2. However, the impact of microorganism colonization on As stem to leaf transport efficiency was not obvious. In summary, inoculation with rhizosphere microbes may increase As accumulation in P. notoginseng root, especially when using bacteria with high As transformation ability. Therefore, it is necessary to evaluate the As transformation capacity before applying biological control microorganism to the rhizosphere of P. notoginseng.

Proteogenomics Study of Blastobotrys adeninivorans TMCC 70007-A Dominant Yeast in the Fermentation Process of Pu-erh Tea.

Blastobotrys adeninivorans plays an essential role in pile-fermenting of Pu-erh tea. Its ability to assimilate various carbon and nitrogen sources makes it available for application in a wide range of industry sectors. The genome of B. adeninivorans TMCC 70007 isolated from pile-fermented Pu-erh tea was sequenced and assembled. Proteomics analysis indicated that 4900 proteins in TMCC 70007 were expressed under various culture conditions. Proteogenomics mapping revealed 48 previously unknown genes and corrected 118 gene models predicted by GeneMark-ES. Ortho-proteogenomics analysis identified 17 previously unidentified genes in B. adeninivorans LS3, the first strain with a sequenced genome among the genus Blastobotrys as well. More importantly, five species specific genes were identified from TMCC 70007, which could serve as a barcode for strain typing and were applicable for fermentation process protection of this industrial species. The datasets generated from tea aqueous extract culture not only increased the proteome coverage and accuracy but also contributed to the identification of proteins related to polyphenols and caffeine, which were considered to change greatly during the microbial fermentation of Pu-erh tea. This study provides a proteome perspective on TMCC 70007, which was considered to be an important strain in the production of Pu-erh tea. The systematic proteogenomics analysis not only made a better annotation on the genome of B. adeninivorans TMCC 70007 as previous proteogenomics study but also provided solution for fermentation process protection on valuable industrial species with species specific genes uniquely identified from proteogenomics study.

Serum protein complex profiling reveals heterogeneity of Balanced constitutional population in traditional Chinese medicine through blue native polyacrylamide gel electrophoresis.

BACKGROUND: Pulse-taking is widely used for diagnosis and treatment in traditional Chinese medicine (TCM), and protein complexes in serum perform various biological functions. The Balanced constitution is one of the major constitutions in TCM, people with Balanced constitution can also share some common characteristics with unbalanced constitution types. METHODS: Blue native polyacrylamide gel electrophoresis (BN-PAGE) was applied to the serum of 25 people with balanced constitutions. The patterns of the protein complexes could be recognized according to the number, molecular weight, and intensity of the gel bands. All of the individual bands from these patterns were cut and in-gel-digested with trypsin, followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis for protein identification and biological function analysis. RESULTS: The protein complex patterns were roughly categorized as type A and B with high stability and reproducibility, and there were 15 and 16 gel bands in type A and type B, respectively. Among the 25 serum samples, 14 belonged to type A, and 11 belonged to type B. High-abundance proteins significantly decreased from 99% to 44% after BN-PAGE separation. The unique proteins in type A were mainly related to lipid metabolism, while the unique proteins in type B were involved in biological processes related to immune response and inflammatory regulation. The Qi-deficiency constitution converted score of type A was higher than that of type B, while the Damp-heat constitution converted score of type A was lower than that of type B. CONCLUSIONS: Our study provided an objective reference for diagnosis and prognosis, which might lay a foundation for establishing the characteristic protein complex spectra of all of the TCM constitutions.

Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval.

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.

The complete chloroplast genome of Aloe vera from China as a Chinese herb.

Aloe vera has been used as a Chinese herb and an ingredient in many cosmetic products in China. In this study, the complete chloroplast genome of A. vera was determined for more genetic data information. The chloroplast genome was 152,875 bp length as a typical quadripartite structure that contained a large single-copy region (LSC) of 83,505 bp, a small single-copy region (SSC) of 16,178 bp and a pair of inverted-repeat regions (IRs) of 26,596 bp. The overall nucleotide composition of chloroplast genome is: 47,185 bp A (30.8%), 48,123 bp T (31.5%), 29,326 bp C (19.2%), 28,241 bp G (18.5%) and the total G + C content of 37.7%. Then, 131 genes were found that included 85 protein-coding genes (PCGs), 38 transfer RNA (tRNAs) and 8 ribosome RNA (rRNAs). The phylogenetic analysis showed that A. vera closely related to A. maculata in the phylogenetic relationship of the family Asphodelaceae by the Maximum-Likelihood (ML) method.

The complete nucleotide sequence of chloroplast genome of Gentiana apiata (Gentianaceae), an endemic medicinal herb in China.

Gentiana apiata N. E. Brown (Gentianaceae) is a perennial herb plant and only grows in Qinba Mountains in China. Here, we first characterized the complete nucleotide sequence of chloroplast (cp) genome of G. apiata via Illumina next generation sequencing platform. The complete chloroplast genome of G. apiata was 144,274 bp in length, comprising of a large single copy (LSC) region of 77,353 bp, a small single copy (SSC) region of 17,009 bp, and two inverted repeat regions (IRs) of 24,956 bp. The cp genome contains 127 genes, including 82 protein-coding genes, 35 tRNA, eight rRNA genes, and two pseudogenes. Phylogenetic analysis based on 18 cp genome sequences showed that G. apiata closely related to congeneric species.

[Effect of Acupuncture on Expression of Glial Fibrillary Acidic Protein in Hippocampus and Prefrontal Cortex and Serum Interleukin-10 in Chronic Restraint Stress Depression Rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of glial fibrillary acidic protein (GFAP) in hippocampus and prefrontal cortex and the level of serum interleukin 10 (IL-10) in rats with depression, so as to explore its mechanism underlying improvement of depression. METHODS: Thirty-two male SD rats were randomly divided into four groups: control, model, acupuncture, and medication (Fluoxetine, Flu) (n=8 rats in each). The depression model was established by using chronic restraint stress (constraint, fasting, water deprivation, etc.) combined with solitary raising for 28 days. Acupuncture was applied to "Baihui" (GV 20) and "Yintang" (GV 29), and bilateral "Sanyinjiao" (SP 6) for 20 min, once daily for 28 days. Fluoxetine (1.8 mg/kg) was given to rats of the medication group by gavage once every day for 28 days. Sucrose consumption test and open field test (crossing and rearing locomotion) were carried out to evaluate the behavioral changes. Western blot was used to detect the expression of GFAP in the hippocampus and prefrontal cortex, and the content of serum IL-10 was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: After modeling, the sucrose consumption, the crossing numbers and rearing times, hippocampal GFAP protein expression and serum IL-10 content were significantly decreased and prefrontal GFAP protein expression was up-regulated markedly in the model group relevant to the control group (P<0.01). After the treatment, the decreased levels of sucrose consumption and crossing numbers, hippocampal GFAP protein expression and serum IL-10 content and the increased prefrontal GFAP protein expression were considerably suppressed in both medication and acupuncture groups compared with the model group (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in increasing the rats' locomotion, sucrose consumption, hippocampal GFAP protein expression (P>0.05) and in down-regulating prefrontal GFAP protein expression (P>0.05 ) except up-regulation of IL-10 level. CONCLUSION: Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in regulating the expression of GFAP in the hippocampal and prefrontal astrocytes, and in increasing the content of serum anti-inflammatory cytokine IL-10.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

OBJECTIVE: To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). BACKGROUND: The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. MATERIALS AND METHODS: Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. RESULTS: Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. CONCLUSIONS: Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison.

OBJECTIVE: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). BACKGROUND: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. METHODS: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. RESULTS: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively (p > 0.05). No patient developed scarring or permanent pigmentation change. LIMITATIONS: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. CONCLUSIONS: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments.

(+)-Borneol suppresses conditioned fear recall and anxiety-like behaviors in mice.

Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors. The present study was to investigate the effects of (+)-Borneol on both contextual and cued fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into ventral hippocampus only reduced 24 h cued fear responses. Moreover, microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed anxiety-like behaviors in the open field test, light/dark exploration and the elevated plus maze test. As selective GABAA receptor antagonist bicuculline reversed the effect of (+)-Borneol on contextual fear paradigm and the drug potentiated GABA-evoked currents in acute hippocampus slices, modulation of the GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety-related disorders.

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.