[Mechanism of Zhongfeng Xingnao Decoction in improving microcirculatory disorders in cerebral hemorrhage based on network pharmacology and molecular docking techniques].

This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components ß-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100ß), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1ß(IL-1ß), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.

Effects of Mindfulness Training Combined with Tai Chi in Patients with Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. One of its crucial therapy approaches is mind-body exercise. Recently, various exercise modalities, including stepping, resistance, aerobics, balance, and whole-body vibration, were investigated to construct the most suitable form of exercise for patients with DPN. The purpose of this study is to describe a standard protocol for mindfulness training combined with Tai Chi. The convenience sampling method was used to select 90 patients with DPN who met the inclusion and exclusion criteria from three communities. The three communities were randomly divided into the control group (CG), the Tai Chi group (TCG), and the mindfulness training combined with the Tai Chi group (MTCG). The CG was given routine health education guidance once a month, a total of three times. Based on the CG, the TCG practiced Tai Chi three times; the MTCG received mindfulness training combined with Tai Chi exercise a week for a total of 12 weeks. Before the intervention and 12 weeks after the intervention, the clinical symptoms, neurological function, attention awareness level, pain, and quality of life of the subjects were evaluated by Toronto Clinical Scoring System (TCSS), Mindful Attention Awareness Scale (MAAS), Visual analog scale (VAS), Diabetes Specificity Quality of life Scale (DSQL) and tumor necrosis factor-α. Overall, the addition of mindfulness training to Tai Chi effectively enhances the exercise effects of Tai Chi. Therefore, mindfulness training combined with Tai Chi is worthy of promotion and application.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Clinical features and prognostic factors of severe cutaneous adverse drug reactions: A single-center retrospective study of 209 cases in China.

BACKGROUND: Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). METHODS: We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n = 46, SJS/TEN, n = 128, AGEP, n = 35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated. RESULTS: Antibiotics ranked first (35.9 %) followed by traditional Chinese medicine (15.8 %) and antiepileptic drugs (14.8 %) among causative drugs of SCAR. One patient (2.2 %) with DRESS and seven patients (5.5 %) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR = 2.340, 95 % CI = 1.192-4.591) and hemoglobin < 100 g/L (OR = 0.126, 95 % CI = 0.016-0.983) were independent risk factors of DRESS. Anemia (OR = 0.191, 95 % CI = 0.037-0.984) and body surface area detached involved at day 1 (OR = 2.749, 95 % CI = 1.115-6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P < 0.05). Lymphocytopenia (OR = 0.004, 95 % CI = 0.000-0.553) was a risk factor of AGEP for acute complications (P = 0.028). CONCLUSION: This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.

[Galangin alleviates learning and memory impairments in APP/PS1 double- transgenic mice by regulating Akt/MEF2D/Beclin-1 signaling pathway].

The study aimed to investigate the effects of galangin on learning and memory impairments and Akt/MEF2 D/Beclin-1 signaling pathway in APP/PS1 double-transgenic mice. The mice in this experiment were divided into the normal group, model group, low-(25 mg·kg~(-1)), medium-(50 mg·kg~(-1)), and high-dose(100 mg·kg~(-1)) galangin groups, donepezil(3 mg·kg~(-1)) group, Akt inhibitor(25 mg·kg~(-1)) group, and autophagy inhibitor(30 mg·kg~(-1)) group, with ten in each group, and administered with the corresponding drugs for 30 successive days. On the 24 th day of medication, the water maze and dark avoidance tests were performed. The levels of p-tau, ß-amyloid peptide 1-42(Aß_(42)), acetylcholinesterase(AChE), ß-site amyloid precursor protein cleaving enzyme 1(BACE1), and amyloid precursor protein(APP) in hippocampus were detected by ELISA, the Beclin-1 mRNA expression by RT-PCR, the expression of Aß_(42) and glial fibrillary acidic protein(GFAP) by immunohistochemistry, and the expression of myocyte enhancer factor 2 D(MEF2 D) by immunofluorescence assay. The pathological changes in hippocampus were observed after HE staining, and the expression of Akt, MEF2 D, and Beclin-1 in hippocampus were assayed by Western blot. These results showed that compared with the normal group, the model group exhibited prolonged swimming time, increased number of errors and electric shocks, up-regulated p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened incubation period, decreased p-Akt and MEF2 D, and obvious hippocampal injury. Compared with the model group, donepezil and galangin shortened the swimming time, reduced the number of errors and electric shocks, down-regulated the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, prolonged the incubation period, up-regulated p-Akt and MEF2 D, and improved the pathological changes in hippocampus. Compared with the autophagy inhibitor group, galangin prolonged the swimming time, elevated the number of errors and electric shocks, enhanced the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened the incubation period, and diminished the expression of p-Akt and MEF2 D. In conclusion, galangin improves the learning and memory impairments and hippocampal neuron injury of APP/PS1 mice, which may be related to its regulation of Akt/MEF2 D/Beclin-1 signaling pathway.

Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking.

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibit the IL-6/STAT3 signaling pathway.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidence indicates that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant to identify novel and valid strains for treating IBD. It has been reported that the probiotic Lactobacillus paracasei L9 (L9), which is identified from the gut of healthy centenarians, can modulate host immunity and plays an anti-allergic role. Here, we demonstrated that L9 alleviates the pathological phenotypes of experimental colitis by expanding the abundance of butyrate-producing bacteria. Oral administration of sodium butyrate in experimental colitis recapitulates the L9 anti-inflammatory phenotypes. Mechanistically, sodium butyrate ameliorated the inflammatory responses by inhibiting the IL-6/STAT3 signaling pathway in colitis. Overall, these findings demonstrated that L9 alleviates the DSS-induced colitis development by enhancing the abundance of butyrate-producing bacterial strains that produce butyrate to suppress the IL-6/STAT3 signaling pathway, providing new insight into a promising therapeutic target for the remission of IBD.

Enhanced biomass and cadmium accumulation by three cadmium-tolerant plant species following cold plasma seed treatment.

Cold plasma seed treatment can promote plant growth and enhance the resistance of agricultural crops to adverse stress. However, the effects of plasma seed treatment on the growth and phytoextraction response of plants to cadmium (Cd) remain poorly documented. Here, we have investigated the feasibility of using plasma seed treatment to enhance the biomass and Cd accumulation of three Cd-tolerant species, namely Bidens pilosa L, Solanum nigrum L. and Trifolium repens L, under different plasma treatment conditions. Possible enhancement mechanisms are also proposed according to the levels of organic acids in the roots and the Cd fractions in rhizosphere soil following different plasma treatment conditions. The optimum plasma power was 100 W (B. pilosa) or 500 W (S. nigrum and T. repens). The optimum plasma exposure time for all three species was 60 s. Plasma seed treatment under the optimum treatment conditions enhanced plant dry biomass by ~17.3-45.0% and Cd accumulation by 8.8-54.4% across all three species compared to the controls. Furthermore, the phytoremediation efficiencies, bioaccumulation factors and transfer factors of the three species also increased significantly after seed plasma treatment. The promotion of plasma treatment on the biomass and Cd accumulation of three species might be due to increased exudation of organic acids from the roots into the rhizosphere soil, thus increasing the concentrations of acid-soluble Cd to form Cd-organic acid complexes that facilitated the uptake and translocation of Cd by the plants. Results of this study revealed that cold plasma seed treatment is an environmentally friendly, economical and efficient means to develop the application of phytoremediation for Cd-contaminated soils.

Network Pharmacology-Based Study on the Active Component and Mechanism of the Anti-Non-Invasive and Invasive Bladder Urothelial Carcinoma Effects of Zhuling Jisheng Decoction.

Zhuling Jisheng decoction is employed for the treatment of bladder urothelial cancer in clinical practice of traditional Chinese medicine. However, there are few studies on its precise mechanism. For the antibladder cancer action of Zhuling Jisheng decoction, a network pharmacological technique was used to design a component/target/pathway molecular regulatory network. The TCMSP dataset was used to identify the chemical makeup of Zhuling Jisheng decoction, which was then analyzed and assessed for oral bioavailability and pharmacological similarity. The chemical composition of Zhuling Jisheng decoction was identified through the TCMSP database, and it was evaluated and screened based on oral bioavailability and drug similarity. The GEO database was searched for genes associated with urothelial bladder carcinoma, and gene targets associated with bladder urothelial cancer resistance were chosen by comparison. The function and linked pathways of the target genes were examined and screened using annotation, visualization, and a comprehensive discovery database. The impact of Zhuling Jisheng decoction on urothelial bladder cancer was studied using Cytoscape software to create a component/target/pathway network. Finally, 69 and 55 target genes were discovered for noninvasive bladder urothelial cancer and invasive bladder urothelial cancer, respectively. In noninvasive urothelial cancer, 118 pathways were highly enriched, including the TNF signaling pathway and the IL-17 signaling route. 103 pathways were highly enriched in invasive urothelial cancer, including the p53 signaling route, bladder cancer route, and calcium signaling route. There were 18 and 15 drug targets associated with noninvasive and invasive bladder urothelial carcinoma prognoses. Many signaling pathways directly act on tumours, and indirect pathways inhibit the development of bladder urothelial carcinoma. This research establishes a scientific foundation for further research into the framework of action of Zhuling Jisheng decoction in the therapy of bladder urothelial cancer.

Efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. It may occur in multiple parts and organs of the patients body, and the lung is the most common. It is a major health threat worldwide. Hepatotoxicity is a common adverse reaction of commonly used clinical anti-tuberculosis drugs, as well as one of the important factors leading to poor prognosis of tuberculosis. Milk thistle is a traditional Chinese medicine extract derived from the mature fruit of Silybum marianum. Clinical practice shows that milk thistle has a good anti-liver injury effect and can be used to prevent anti-tuberculosis drug-induced liver injury. However, there is a lack of evidence-based medicine. The research carried out in this protocol is to systematically evaluate the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and to improve the evidence-based basis for clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury. METHOD: Computer search of English databases (PubMed, the Cochrane Library, Embase, Web of Science) and Chinese databases (CNKI, VIP, Wanfang, China Biology Medicine disc (CBMdisc)) was performed. From the establishment of database to October 2020, 2 researchers independently extracted and evaluated the data included in the randomized controlled clinical research of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and used RevMan5.3 software to conduct a meta-analysis of the included literature. RESULT: In this research, the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury were evaluated by indicators such as the incidence of liver injury, bilirubin levels, and liver enzyme levels. CONCLUSION: In this research, reliable evidence-based evidence for the clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury was provided. OSF REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/VC3RM.

Neferine alleviates memory and cognitive dysfunction in diabetic mice through modulation of the NLRP3 inflammasome pathway and alleviation of endoplasmic-reticulum stress.

Accumulating clinical and epidemiological evidence indicates a close relationship between diabetes mellitus and dysfunction in memory and cognition. Neferine (NE) is a unique bis-benzylisoquinoline alkaloid derived from the seed embryo of Nelumbo nucifera (Lotus), an herbal medicine with a long history of use in used in China. NE has been reported to ameliorate diabetes mellitus and exert considerable protective effects on the central nervous system. Thus, this study aimed to investigate the effects of NE on memory and cognitive dysfunction in db/db mouse model of diabetes. First, we found that NE treatments significantly ameliorated behavioral impairment and cognitive dysfunction in the Morris water maze, Y-maze, and fear conditioning test in db/db mice. Additionally, in these diabetic mice, NE decreased fasting glucose and insulin resistance while promoting lipid metabolism. Furthermore, NE treatments alleviated oxidative stress and inhibited inflammatory responses in the hippocampus. Further investigations showed that NE suppressed the NOD-like receptor protein 3 (NLRP3) inflammasome pathway via down-regulating the levels of thioredoxin-interacting protein (TXNIP), NLRP3 inflammasomes, apoptosis-associated speck-like protein containing a CARD (ASC), and mature interleukin-1ß (IL-1ß) in the hippocampus. Moreover, NE alleviated endoplasmic-reticulum (ER) stress via down-regulating the levels of immunoglobulin heavy-chain-binding protein (GRP78), C/EBP homologous protein (CHOP), proteins kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) in the hippocampus. In conclusion, these results suggest that NE ameliorated memory and cognitive dysfunction, possibly through modulating the NLRP3 inflammasome pathways and alleviating ER stress.

HIV Vaccine Preparedness among Men Who Have Sex with Men in Taiwan: Sociocultural and Behavioral Factors.

In Taiwan, men who have sex with men (MSM) are at disproportionate risk of HIV infection. We examined awareness and acceptability of future HIV vaccines. From July to August 2014, we conducted a cross-sectional survey with MSM recruited through community-based organizations (CBOs) in 2 cities. Among 200 participants (mean age, 27.6 years), half reported multiple partners and one-third condomless anal sex (past 3 months); 12% were HIV-positive. Traditional Chinese medicine (TCM) use was reported by 42.7%. Over two-thirds (69.0%) were aware of HIV vaccine research, but less than half (43.8%) would accept an HIV vaccine if available. In multivariable analysis, higher educational attainment, >5 sex partners, and TCM use were positively associated with HIV vaccine awareness. Culturally informed HIV vaccine preparedness in Taiwan may be supported by a complementary approach to TCM and HIV prevention technologies, tailoring information for MSM with lower education and targeting those at high risk through gay-identified CBOs.

A Phenylselenium-Substituted BODIPY Fluorescent Turn-off Probe for Fluorescence Imaging of Hydrogen Sulfide in Living Cells.

Herein a phenylselenium-substituted BODIPY (1) fluorescent turn-off sensor was developed for the purpose to achieve excellent selectivity and sensitivity for H2S detection based on the substitution reaction of the phenylselenide group at the 3-position with H2S. The excess addition of hydrogen sulfide promoted further substitution of the phenylselenide group at the 5-position of the probe and was accompanied by a further decrease in fluorescence emission intensity. Sensor 1 demonstrated remarkable performance with 49-fold red color fluorescence intensity decrease at longer excitation wavelength, a low detection limit (0.0025 µM), and specific fluorescent response toward H2S over anions, biothiols, and other amino acids in neutral media. It showed no obvious cell toxicity and good membrane permeability, which was well exploited for intracellular H2S detection and imaging through fluorescence microscopy imaging.

An updated dose-response meta-analysis of coffee consumption and liver cancer risk.

Prospective cohort studies of the relationship between coffee consumption and liver cancer risk have drawn different conclusions. Therefore, a dose-response meta-analysis of prospective cohort studies was performed to disentangle this causal relationship. Prospective cohort studies of the association between coffee consumption and liver cancer risk published prior to Jan 9, 2016 were identified by searching in the PubMed and EMBASE databases. Extracted data were analyzed using a random-effects model. Of the 2892 records identified using the search strategy, a total of twenty cohort studies from ten publications were included in the final meta-analysis. The pooled estimate of relative risk (RR) with 95% confidence interval (CI) for highest vs. non/occasional coffee drinkers was 0.55(0.44-0.67). No evidence of publication bias was observed (p for Egger's test = 0.229). Sensitivity analysis indicated the results were robust. Dose-response analysis revealed a significant linear dose-response relationship between coffee consumption and liver cancer risk (p = 0.36). Subgroup analyses stratified by pre-specified variables (gender, geographic region, and adjusted factors) indicated similar results within individual subgroups. Our meta-analysis suggested that coffee consumption is inversely associated with liver cancer risk.

The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats.

Angelica sinensis (AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus.

Acupuncture for amnestic mild cognitive impairment: a meta-analysis of randomised controlled trials.

OBJECTIVE: Mild cognitive impairment (MCI) is a pre-dementia state; 5-10% of cases per year will evolve into dementia. MCI can be amnestic (AMCI) or non-amnestic. AMCI is associated with a higher risk of progression. In recent years, interest in acupuncture as a potential treatment for AMCI has grown. The aim of this meta-analysis was to estimate the clinical effectiveness and safety of acupuncture for AMCI. METHODS: Randomised controlled trials (RCTs) of acupuncture versus medical treatment for AMCI were identified using the following databases from inception to July 2015: PubMed; Medline; CENTRAL; Chinese Scientific Journal Database; The Chinese Acupuncture Trials Register; China National Knowledge Infrastructure (CNKI); and Wanfang database. Data were extracted from RCTs meeting the inclusive criteria according to Cochrane methods. Meta-analyses were conducted using Rev Man V.5.3 software. RESULTS: Five trials involving 568 subjects were included. Meta-analysis showed that participants receiving acupuncture had better outcomes than those receiving nimodipine with greater clinical efficacy rates (odds ratio (OR) 1.78, 95% CI 1.19 to 2.65; p<0.01), mini-mental state examination (MMSE) scores (mean difference (MD) 0.99, 95% CI 0.71 to 1.28; p<0.01), and picture recognition score (MD 2.12, 95% CI 1.48 to 2.75; p<0.01). Meta-analysis also showed acupuncture in conjunction with nimodipine significantly improved MMSE scores (MD 1.09, 95% CI 0.29 to 1.89; p<0.01) compared to nimodipine alone. Three trials reported adverse events. Methodological quality of the included studies was judged to be generally poor. CONCLUSIONS: Acupuncture appears effective for AMCI when used as an alternative or adjunctive treatment; however, caution must be exercised given the low methodological quality of included trials. Further, more rigorously designed studies are needed.

[Constituents from Ranunculus ternatus and Their Inhibitory Effects on Multidrug-Resistant Tuberculosis].

Objective: To explore the chemical constituents of Ranunculus ternatus and their inhibitory effects on multidrug-resistant tuberculosis. Methods: All compounds were separated by silica gel, Sephadex LH-20 column chromatography etc. Their structures were identified by NMR spectroscopy. The absolute concentration method was used for susceptibility test on multidrug-resistant tuberculosis strains with Ranunculus ternatus. Results: Seven compounds were isolated and identified as 2-deoxy-D-ribono-1,4-lactone( 1),isomaltol-α-D-glucoside( 2),vanillic acid-4-O-ß-D-glucopyranoside( 3), salicoside( 4),n-butyl-ß-D-fructofuranoside( 5),3,4-dimethoxybenzoic acid( 6),and caffeic acid( 7). Conclusion: Compounds 1 ~ 6 are isolated from this genus for the first time. All compounds except 5 of Ranunculus ternatus reveal modest activity to inhibit multidrug-resistant tuberculosis.

[Isolation and structural identification of flavonoids from Aurantii Fructus].

Aurantii Fructus is the dried and immature fruit of Citrus aurantium and its cultivars. To investigate the chemical constituents of Aurantii Fructus, the separation and purification of constituents were performed by column chromatography on silica gel LH-20, HW-40, ODS, PHPLC and PTLC. Fourteen flavonoids, including four flavone glycosides and ten polymethoxyflavones (PMFs) were isolated from the EtOAc fraction and Petroleum ether fraction of Aurantii Fructus and their structures were identified by physicochemical properties and spectral data (NMR and MS) as (2R) -and (2S)-6"-O-acetylprunin (1,2), naringenin-7-O-ß-D-glucopyranside (3), 5,7,4'-trihydroxy-8,3'-dimethoxyflavone-3-O-6"-(3-hydroxyl-3-methylglutaroyl)-ß-D-glucopyranoside(4), 4'-hydroxy-5,6, 7-trimethoxyflavone (5), natsudaidain (6), nobiletin (7), sinensetin (8), 5,6,7,4'-tetramethoxyflavone (9), 5,7,8,4'-tetramethoxyflavone (10), 3,5,6,7,8,3',4'-heptamethoxyflavone (11), tangeretin (12), 5-demethyl nobiletin (13), and 5-hydroxy-6,7,3', 4'-tetramethoxyflavone (14). Compound 3-5 s were isolated from this plant for the first time and compound 1 was a new one.

Radix Angelica Sinensis Promotes Synaptic Plasticity During Cognitive Recovery in Chronically Stressed Rats.

The accumulation of chronic stress is associated with cognitive dysfunction. Radix Angelica Sinensis (RAS) has been shown to have neuroprotective potential for treating Alzheimer's disease and vascular dementia. However, the impact of RAS on cognitive impairment induced by chronic stress has not been studied. In the present study, RAS significantly alleviated cognitive deficits in rats subjected to chronic restraint stress. This neuroprotective effect was associated with enhancement of synaptic efficacy by improving field excitatory postsynaptic potential amplitudes, alleviating adverse alterations in the structure of synapses and neurons in the hippocampus, and increasing the levels of brain-derived neurotrophic factor, microtubule-associated protein-2, and synaptophysin in the hippocampus. These findings provide initial evidence for the therapeutic potential of RAS for the treatment of neuronal deterioration caused by chronic stress.