Traditional Chinese Medicine Shi-Bi-Man ameliorates psoriasis via inhibiting IL-23/Th17 axis and CXCL16-mediated endothelial activation.

BACKGROUND: Psoriasis is a chronic inflammatory genetic disease, mainly manifesting in the skin. Conventional therapies, such as glucocorticosteroids and corticosteroids, have adverse effects that limit drug use. Hence, it is imperative to identify a new therapeutic strategy that exhibits a favorable safety profile. Shi-Bi-Man (SBM) is a safe herbal supplement sourced from various natural plants, including ginseng, angelica sinensis, polygonum multiflorum, and aloe vera. PURPOSE: We aimed to find a potential treatment for psoriasis and investigate the underlying mechanism through which SBM alleviates psoriatic-like skin inflammation in mice. METHODS: We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis. The changes in body weight and Psoriasis Area and Severity Index (PASI) score were recorded throughout the entire process. Additionally, we used hematoxylin-eosin staining to observe the skin structure and performed single-cell RNA sequencing to explore the underlying mechanism of SBM in influencing the psoriasis-like phenotype. Immunofluorescence was conducted to verify our findings. Furthermore, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to investigate the impact of Tetrahydroxy stilbene glycoside (TSG) on the expression levels of IL23 in HaCaT cells. RESULTS: SBM remarkably alleviated the psoriasis-like phenotype by inhibiting IL-23/Th17 cell axis. Single-cell RNA sequencing analysis revealed a decrease in the expression of Il17 and Il23 in keratinocytes and T cells, concomitant with a reduction in the proportion of Th17 cells. Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

Preventive effect and mechanism of Tibetan tea extract on thrombosis in arachidonic acid-induced zebrafish determined via RNA-seq transcriptome profiles.

Thrombosis is a key pathological event in cardiovascular diseases and is also the most important targeting process for their clinical management. In this study, arachidonic acid (AA) was used to induce thrombus formation in zebrafish larvae. Blood flow, red blood cell (RBCs) aggregation and cellular oxidative stress were measured to evaluate the antithrombotic effect of Tibetan tea (TT). Meanwhile, the potential molecular mechanism was further explored by transcriptome sequencing (RNA-seq). The results indicated that TT could significantly restore heart RBCs intensity of thrombotic zebrafish, whilst decreasing RBCs accumulation in the caudal vein. The transcriptome analysis revealed that the preventive effect of TT on thrombosis could be mostly attributed to changes in lipid metabolism related signaling pathways, such as fatty acid metabolism, glycerollipid metabolism, ECM-receptor interaction and steroid biosynthesis signaling pathway. This study demonstrated that Tibetan tea could alleviate thrombosis by reducing oxidative stress levels and regulating lipid metabolism.

Medication use and comorbidities in an increasingly younger osteoarthritis population: an 18-year retrospective open-cohort study.

OBJECTIVES: As understanding of the pathogenesis and treatment strategies for osteoarthritis (OA) evolves, it is important to understand how patient factors are also changing. Our goal was to examine demographics and known risk factors of patients with OA over time. DESIGN: Open-cohort retrospective study using electronic health records. SETTING: Large US integrated health system with 7 hospitals, 2.6 million outpatient clinic visits and 97 300 hospital admissions annually in a mostly rural geographic region. PARTICIPANTS: Adult patients with at least two encounters and a diagnosis of OA or OA-relevant surgery between 2001 and 2018. Because of geographic region, over 96% of participants were white/Caucasian. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive statistics were used to examine age, sex, body mass index (BMI), Charlson Comorbidity Index, major comorbidities and OA-relevant prescribing over time. RESULTS: We identified 290 897 patients with OA. Prevalence of OA increased significantly from 6.7% to 33.5% and incidence increased 37% (from 3772 to 5142 new cases per 100 000 patients per year) (p<0.0001). Percentage of females declined from 65.3% to 60.8%, and percentage of patients with OA in the youngest age bracket (18-45 years) increased significantly (6.2% to 22.7%, p<0.0001). The percentage of patients with OA with BMI ≥30 remained above 50% over the time period. Patients had low comorbidity overall, but anxiety, depression and gastro-oesophageal reflux disease showed the largest increases in prevalence. Opioid use (tramadol and non-tramadol) showed peaks followed by declines, while most other medications increased slightly in use or remained steady. CONCLUSIONS: We observe increasing OA prevalence and a greater proportion of younger patients over time. With better understanding of how characteristics of patients with OA are changing over time, we can develop better approaches for managing disease burden in the future.

Effects of concentration-dependent graphene on maize seedling development and soil nutrients.

The long-term use of chemical fertilizers to maintain agricultural production has had various harmful effects on farmland and has greatly impacted agriculture's sustainable expansion. Graphene, a unique and effective nanomaterial, is used in plant-soil applications to improve plant nutrient uptake, reduce chemical fertilizer pollution by relieving inadequate soil nutrient conditions and enhance soil absorption of nutrient components. We investigated the effects of graphene amendment on nutrient content, maize growth, and soil physicochemical parameters. In each treatment, 5 graphene concentration gradients (0, 25, 50, 100, and 150 g kg-1) were applied in 2 different types (single-layer and few-layers, SL and FL). Soil aggregates, soil accessible nutrients, soil enzyme activity, plant nutrients, plant height, stem diameter, dry weight, and fresh weight were all measured throughout the maize growth to the V3 stage. Compared to the control (0 g kg-1), we found that graphene increased the percentage of large agglomerates (0.25-10 mm) in the soil and significantly increased the geometric mean diameter (GMD) and mean weight diameter (MWD) values of > 0.25 mm water-stable agglomerates as the increase of concentration. Soil available nutrient content (AN, AP, and AK) increased, peaking at 150 g kg-1. Graphene boosted nutrient absorption by maize plants, and aboveground total nitrogen (TN), total phosphorus (TP), and total potassium (TK) contents rose with the increasing application, which raised aboveground fresh weight, dry weight, plant height, and stalk thickness. The findings above confirmed our prediction that adding graphene to the soil may improve maize plant biomass by enhancing soil fertility and improving the soil environment. Given the higher manufacturing cost of single-layer graphene and the greater effect of few-layer graphene on soil and maize plants at the same concentration, single-layer graphene and few-layer graphene at a concentration of 50 g kg-1 were the optimal application rates.

Metabolomic Analysis of Fermented Tibetan Tea Using Bacillus circulans and Their Biological Activity on Mice via the Intestine-Hepatic Axis.

The use of Bacillus circulans as the sole starter provides better process control compared to natural fermentation. However, the chemical composition of fermented Tibetan tea by B. circulans and its regulatory effects on the intestine-liver axis has not been reported. For this purpose, a high-resolution liquid chromatography tandem mass spectrometry metabolomics approach was performed. The effects of fermented Tibetan tea on the intestine-liver axis of mice were also evaluated. Untargeted metabolomics analysis showed that the contents of catechin derivatives, flavonoids, phenolic acids, and terpenoids increased by 0.3, 2.38, 2.65, and 3.36%, respectively, compared with those before fermentation. Furthermore, 16S ribosomal RNA sequence analysis revealed that the relative abundance of Lactobacillus spp. in the intestine increased after consumption of fermented tea. Additionally, based on histological and quantitative PCR analyses, fermented Tibetan tea also improved intestinal development and intestinal barrier function in mouse, while increasing the antioxidant capacity of mouse liver. Thus, fermented Tibetan tea could provide beneficial health effects through the intestine-liver axis. These findings have facilitated the study of the chemical composition of Tibetan tea and provided theoretical support for its use as a natural beverage with intestinal probiotic functions.

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Analysis of Blueberry Plant Rhizosphere Bacterial Diversity and Selection of Plant Growth Promoting Rhizobacteria.

Microbial metabolites in rhizosphere soil are important to plant growth. In this study, microbial diversity in blueberry plant rhizosphere soil was characterized using high-throughput amplicon sequencing technology. There were 11 bacterial phyla and three fungal phyla dominating in the soil. In addition, inorganic-phosphate-solubilizing bacteria (iPSB) in the rhizosphere soil were isolated and evaluated by molybdenum-antimony anti-coloration method. Their silicate solubilizing, auxin production, and nitrogen fixation capabilities were also determined. Eighteen iPSB in the rhizosphere soil strains were isolated and identified as Buttiauxella, Paraburkholderia and Pseudomonas. The higher phosphorus-solubilizing capacity and auxin production in blueberry rhizosphere belonged to genus Buttiauxella sp. The strains belong to genus Paraburkholderia had the same function of dissolving both phosphorus and producing auxin, as well as silicate and nitrogen fixation. The blueberry seeds incubated with the strains had higher germination rates. The results of this study could be helpful in developing the plant growth-promoting rhizobacteria (PGPR) method for enhancing soil nutrients to blueberry plant.

Associations of Healthcare Utilization and Costs with Increasing Pain and Treatment Intensity Levels in Osteoarthritis Patients: An 18-Year Retrospective Study.

INTRODUCTION: Osteoarthritis (OA) is a complex disease, and prior studies have documented the health and economic burdens of patients with OA compared to those without OA. Our goal was to use two strategies to further stratify OA patients based on both pain and treatment intensity to examine healthcare utilization and costs using electronic records from 2001 to 2018 at a large integrated health system. METHODS: Adult patients with ≥1 pain numerical rating scale (NRS) and diagnosis of OA were included. Pain episodes of ≥90 days were defined as mild (0-3), moderate (4-6), or severe (7-10) based on initial NRS. Patients were initially classified as mild and moved to moderate-severe OA if any of eight treatment-based criteria were met. Outpatient visits (OP), emergency department visits (ED), inpatient days, and healthcare costs (both all-cause and OA-specific) were compared among pain levels and OA severity levels as frequencies and per-member-per-year rates, using generalized linear regression models adjusting for age, sex, and body mass index, with contrasts of p < 0.05 considered significant. RESULTS: We identified 127,656 patients, 92,576 with pain scores. Moderate and severe pain were associated with significantly higher rates of OA-related utilization and costs, and all-cause ED visits and pharmacy costs. Moderate-severe OA patients had significantly higher OA-related utilization and costs, and all-cause OP, ED and pharmacy costs. CONCLUSIONS: Pain and treatment intensity were both strongly associated with OA-related utilization but not consistently with all-cause utilization. Our results provide promising evidence of better criteria and approaches for predicting disease burden and costs in the future.

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A reduction of chemical fertilizers and improving fertilizer utilization rate are important for ensuring a balance between plant growth and minimizing the degradation of the black soil. We conducted a 2-year pot experiment with four treatments during 2019 and 2020, including T0: no fertilizer, T1: conventional use of chemical fertilizer, T2: 15% reduction of the chemical fertilizer combined with 400 kg·hm-2 of humic acid bio-fertilizer (HABF), and T3: 30% reduction of the chemical fertilizer combined with 600 kg·hm-2 of HABF, to examine the effect of reduction rates of chemical fertilizers combined with the HABF on soil microbial abundance, enzyme activity and nutrient content in maize cultivation. The results showed that the application of HABF significantly increased the abundance of soil bacteria and fungi, with the number of microbial colonies being positively correlated with the amount of HABF. When measured at the tassel stage of maize growth, T2 and T3 treatments significantly increased the activities of urease, sucrase, and catalase in soil by 11.4%-21.6%, 34.9%-46.7%, and 6.5%-13.4%, respectively. The available nitrogen contents in T2 and T3 treatments were higher than that in the T1 treatment by 8.2%-18.1%, which ensured the sufficient nitrogen supply to maize after the tassel stage. Soil available phosphorus and available potassium contents increased by 17.1%-121.0% and 9.6%-57.3%, respectively, compared with T1 treatment. With the increases of the amount of HABF, the activation effects of soil phosphorus and potassium and dry matter mass per plant increased significantly in T2 and T3 treatments compared with T1 treatment. In conclusion, HABF promoted the proliferation of soil bacteria and fungi, improved activities of catalase, urease, and sucrase, soil nutrient contents, and dry matter mass per plant. The 15% reduction of chemical fertilizer combined with 400 kg·hm-2 of HABF is the most suitable nutrient management strategy for maize production in black soil.

The Impact of Non-Invasive Ventilation Combined with Montelukast on Clinical Efficiency and Pulmonary Function in Patients with Bronchial Asthma Complicated by Obstructive Sleep Apnea Hypopnea Syndrome.

PURPOSE: Our study aims to explore the impact of non-invasive ventilation (NIV) alone or combined with montelukast on clinical efficiency and pulmonary function (PF) in treating patients with bronchial asthma complicated by obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 386 patients with bronchial asthma underwent sleep monitoring. Patients were divided into 3 groups according to the different treatment methods. The changes in PF, apnea hypopnea index (AHI) score and the level of inflammatory factors in all patients before and after treatment were recorded, and the clinical effect following treatment was noted. RESULTS: Following treatment, the clinical efficiency of Group 2 was significantly better than that of both Group 1and the control group, and the therapeutic effect in Group 1 was better than in the control group (P < .05). Before treatment, vital capacity (VC), peak expiratory flow (PEF), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and asthma control test (ACT) scores, AHI scores, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) index were compared between the 3 groups (P > .05). In contrast, after treatment the VC, PEF, FEV1/FVC and ACT, AHI, CRP and TNF-α scores and the IL-6 index in the 3 groups were improved compared with before treatment. The indices in Groups 1 and 2 were better than in the control group, and the VC, PEF, FEV1/FVC and ACT, AHI, CRP, and TNF-α scores and IL-6 index in Group 2 reported greater beneficial effect than in Group 1. CONCLUSION: The combination of NIV and montelukast exerts a beneficial effect in treating patients with bronchial asthma complicated with OSAHS, which holds the potential of effectively improving clinical symptoms and PF, reducing ACT and AHI scores and alleviating inflammatory reactions. Hence, the combination is valid and appropriate for clinical application.

Characterizing primary care for patients with major depressive disorder using electronic health records of a US-based healthcare provider.

BACKGROUND: Major depressive disorder (MDD) is predominantly managed in primary care. However, primary care providers (PCPs) may not consistently follow evidence-based treatment algorithms, leading to variable patient management that can impact outcomes. METHODS: We retrospectively analyzed adult patients with MDD seen at Geisinger, an integrated health system. Utilizing electronic health record (EHR) data, we classified patients as having MDD based on International Classification of Disease (ICD)-9/10 codes or a Patient Health Questionnaire (PHQ)-9 score ≥5. Outcomes assessed included time to first visit with a PCP or behavioral health specialist following diagnosis, antidepressant medication switching, persistence, healthcare resource utilization (HRU), and treatment costs. RESULTS: Among the 38,321 patients with MDD managed in primary care in this study, significant delays between diagnosis with antidepressant prescribing and follow-up PCP visits were observed. There was also considerable variation in care following diagnosis. Overall, 34.9% of patients with an ICD-9/10 diagnosis of MDD and 41.3% with a PHQ-9 score ≥15 switched antidepressants. An ICD-9/10 diagnosis, but not moderately severe to severe depression, was associated with higher costs and HRU. More than 75% of patients with MDD discontinued antidepressant medication within 6 months. LIMITATIONS: The study population was comparable with other real-world studies of MDD, but study limitations include its retrospective nature and reliance on the accuracy of EHRs. CONCLUSIONS: Management of patients with MDD in a primary care setting is variable. Addressing these gaps will have important implications for ensuring optimal patient management, which may reduce HRU and treatment medication costs, and improve treatment persistence.

Integrated care is associated with increased behavioral health access and utilization for youth in crisis.

INTRODUCTION: Pediatric integrated care is well-positioned to play a substantial role in crisis intervention; however, few studies have investigated the impact of these services. METHOD: We investigated differences in service utilization for youth experiencing a crisis in a large, predominantly rural health system by comparing outcomes for 171 youth who received a crisis evaluation in a primary care behavioral health (PCBH) setting to 171 youth presenting to the emergency department at the main hospital campus using a retrospective cohort study design. RESULTS: PCBH patients were less likely to be male, more likely to be diagnosed with an Adjustment Disorder and less likely to be diagnosed with Autism Spectrum Disorder. Youth evaluated in PCBH were more likely to receive a psychiatric admission, had a shorter latency to the next BH appointment, and had higher rates of completing at least 1 visit in the year following the evaluation. A statistically nonsignificant reduction in frequency of psychiatric admission was observed in the year after the index date, with 3 integrated care patients (vs. 18 on index date) and 5 ED patients (vs. 6 on index date) admitted. DISCUSSION: Opportunities for future research on cost-effectiveness of care and continuous improvement aligned with quadruple aim outcomes are discussed. Overall, this study is among few others investigating the potential for pediatric integrated care models to contribute to youth suicide prevention and the study demonstrated promising increases in access and engagement with timely behavioral health care. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase.

Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle's centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis. As a result, BP-treated cells exhibit multipolar spindles and mitotic delay, and ultimately undergo apoptosis. Mechanistically, BP compromises centrosome integrity by deactivating the centrosome kinase polo-like kinase 1 (PLK1). BP directly binds to PLK1, inducing its aggregation, decreasing its cytosolic mobility and eventually restricting its recruitment to centrosomes for activation. With this mechanism, BP nanomaterials show great anticancer potential in tumour xenografted mice. Together, our study reveals a molecular mechanism for the tumoricidal properties of BP and proposes a direction for biomedical application of nanomaterials by exploring their intrinsic bioactivities.

Efficacy of magnesium sulfate as an adjuvant to rocuronium in general anaesthesia: a meta-analysis.

OBJECTIVE: Magnesium sulfate is considered to be an effective adjuvant to rocuronium in general anaesthesia. We conducted a meta-analysis to clarify its efficacy. METHODS: We searched the PubMed, Embase, Web of Science, Cochrane Library, WanFang, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) of magnesium sulfate as an adjuvant to rocuronium from the start of the database establishment until May 2020. RESULTS: Eleven RCTs were analysed. The pooled meta-analysis showed that using magnesium sulfate as an adjuvant significantly shortened the onset time and prolonged the clinical duration of neuromuscular blockade by rocuronium compared with the control group without magnesium sulfate. However, there was no significant difference in recovery index of neuromuscular block between the magnesium and control groups. Furthermore, magnesium sulfate significantly increased the rates of excellent and clinically acceptable intubation conditions. CONCLUSION: Adding magnesium sulfate to rocuronium during general anaesthesia can alter the neuromuscular parameters, including shortening the anaesthesia-onset time and prolonging the clinical duration, without significantly increasing the recovery time. Pretreatment with magnesium sulfate may also improve intubation conditions during general anaesthesia.

Medial septum glutamatergic neurons control wakefulness through a septo-hypothalamic circuit.

The medial septum (MS) is involved in arousal-based behaviors and modulates general anesthesia response. However, the role of MS in wakefulness control remains unknown. Here, combining double fluorescence in situ hybridization and optrode recording, we showed that MS glutamatergic neurons exhibited higher activities preferentially during wakefulness. Activating these neurons, either optogenetically or chemogenetically, strongly promoted wakefulness, mainly through the transition from non-rapid eye movement (NREM) sleep to wakefulness. In contrast, inactivation of these neurons reduced wakefulness by the transition from wakefulness to NREM sleep. Furthermore, both rabies-mediated monosynaptic retrograde and anterograde tracing showed that MS glutamatergic neurons monosynaptically innervated lateral hypothalamus (LH) glutamatergic neurons, which were also wake-active as well as wake-promoting. Activating MS-derived glutamatergic terminals in LH enhanced wakefulness, whereas silencing MS glutamatergic neurons destabilized the wake-active preference of LH glutamatergic neurons. These results reveal a vital role of MS glutamatergic neurons in wakefulness control and depict a novel septo-hypothalamic circuit for wakefulness.

Green Tea Polyphenols Protect against Acetaminophen-Induced Liver Injury by Regulating the Drug Metabolizing Enzymes and Transporters.

Green tea polyphenols (GTPs) have been shown to exhibit diverse beneficial effects against a variety of diseases. Acetaminophen (APAP) overdose is one of the most frequent causes of drug-induced liver injury. In the current study, we aimed to investigate the protective effect of GTP on APAP-induced liver injury in mice and the underlying mechanisms involved. Male C57BL/6J mice were treated orally with different doses of GTP (37.5, 75, or 150 mg/kg) 4 h after APAP overdose (400 mg/kg) and continuously given every 8 h until sacrificed at 4, 12, 20, and 48 h after the first treatment of GTP. Survival rate and histological and biochemical assessments were performed to evaluate the APAP-induced liver injury. Protein expression of multiple drug metabolizing enzymes and transporters was measured to demonstrate the possible mechanisms involved. Our results revealed that administration of different doses of GTP significantly alleviated APAP-induced liver injury by improving the survival rate, hepatocellular necrosis, and ALT/AST/GSH levels after APAP overdose (400 mg/kg). The protein expression of APAP-induced drug transporters and metabolizing enzymes was mostly induced by GTP treatment, which was followed by reduction in drug transporters at the later time points. The current study collectively demonstrated that GTP protects against APAP-induced liver injury, possibly through regulating drug metabolizing enzymes and transporters after APAP overdose.

Characterizations of microbial diversity and machine oil degrading microbes in machine oil contaminated soil.

Microbial diversity in machine oil contaminated soil was determined by high-throughput amplicon sequencing technology. The diversity of culturable microbes in the contaminated soil was further characterized using polymerase chain reaction method. Proteobacteria and Bacteroidetes were the most dominant phyla and occupied 52.73 and 16.77%, respectively, while the most abundant genera were Methylotenera (21.62%) and Flavobacterium (3.06%) in the soil. In the culturable microbes, the major phyla were Firmicutes (46.15%) and Proteobacteria (37.36%) and the most abundant genera were Bacillus (42.86%) and Aeromonas (34.07%). Four isolated microbes with high machine oil degradation efficiency were selected to evaluate their characteristics on the oil degradation. All of them reached their highest oil degradation rate after 7 days of incubation. Most of them significantly increased their oil degradation rate by additional carbon or organic nitrogen source in the incubation medium. The oil degradation rate by combination of the four microbes at the same inoculation level was also higher than the rate from each individual microbe. The protocol and findings of this study are very useful for developing micro-bioremediation method to eliminate machine oil contaminants from soil.

Application of quadrupole-Orbitrap high-resolution mass spectrometry in rapid screening and identification of synthetic dyes in herbal medicines.

In this work, a method combining ultra-high performance liquid chromatography and hybrid quadrupole-Orbitrap high-resolution mass spectrometry (HR-MS) was developed and validated for use in the simultaneous screening, identification, and quantification of 21 synthetic dyes in herbal medicines. To optimize the chromatographic conditions, we used a combined Full mass scan and data-dependent MS/MS (Full MS/dd-MS2) approach in positive and negative ion mode. Under this mode, selected ions with given fragmentation energy were subjected to a dd-MS2 scan following a Full MS scan. The selectivity of this method was effectively improved using 70,000 full width at half maximum mass resolution and narrow mass window (typically 5 ppm), and a single injection was sufficient for simultaneous identification and quantification of 21 synthetic dyes within 10 min. The combined method was fully validated and complies with all criteria for selectivity, sensitivity, calibration curve linearity, accuracy, precision, recovery, matrix effect, and stability. All analytes showed excellent linear relationships as all the coefficients of determination (r2) are greater than 0.9978 over wide ranges of concentrations (e.g. 1.0-500 ng/mL for sunset yellow). The validated method was employed to detect synthetic dyes in herbal medicines and was demonstrated to provide a reliable technical basis for drug regulation and public health protection.

Aroma characterization of Hanzhong black tea (Camellia sinensis) using solid phase extraction coupled with gas chromatography-mass spectrometry and olfactometry and sensory analysis.

The unique aroma of the Hanzhong black tea is due to the special location of the harvesting place and specific manufacturing processes. In this study, a solid phase extraction method (SPE) as sample preparation tool was combined with gas chromatography (GC) as separation technique and several detection systems such as mass spectrometry (MS), flame ionization (FID) and olfactometry (O), which, together with sensorial analysis were used to characterize aroma compounds in Hanzhong black tea infusion. Seventy three aroma compounds were identified and quantified in the tea infusion by the GC-MS and GC-FID methods, respectively. Among them, odor perceptions of 24 compounds were characterized by the GC-O analysis. It was found that linalool oxide I, II and III, E,E-2,4-nonadienal, 4,5-dimethyl-3-hydroxy-2,5-dihydrofuran-2-one, 1-octen-3-one, E,Z-2,6-nonadienal, bis(2-methyl-3-furyl) disulfide had higher odor activity value in the tea infusion and offered floral, fatty, and caramel, mushroom, cucumber, and cooked beef -like odors, respectively. Overall, floral and mushroom and caramel -like odors significantly dominated in the Hanzhong black tea infusion.

Reversing effects of ginsenosides on LPS-induced hepatic CYP3A11/3A4 dysfunction through the pregnane X receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer), a traditional Chinese medicine, is widely used in the adjunctive therapy of the liver diseases. AIM OF THE STUDY: Ginsenosides are one kind of the main active ingredients in ginseng. Although hepatoprotective mechanisms of ginsenosides, such as anti-oxidation, anti-inflammation and anti-apoptosis, have been well studies, little is known about the effect of ginsenosides on drug metabolism in liver. Since CYP3A11/3A4 is a major enzyme catalyzing the drug metabolism in liver, an investigation of the enzyme's expression during the progression of a liver disease will gain valuable information about the hepatic drug metabolism. The purpose of this study was to determine the effect of ginsenosides on the expression of hepatic CYP3A11/3A4 in the lipopolysaccharides (LPS) injured human HepG2 cells and mice. We hypothesize that ginsenosides are important to stabilize CYP3A11/3A4 expression in an injured liver. MATERIALS AND METHODS: In this study, LPS was intraperitoneally intermittently injected to induce the liver injury in mice. Ginsenosides were intragastrically administered to mice for 7 days to treat the liver injury. Serum biochemical analysis and histopathological study were taken to evaluate the hepatoprotective effect of ginsenosides. The effect of ginsenosides was also evaluated in human HepG2 cells in the presence and absence of LPS. Real-time PCR and western blotting method were used to detect the mRNA and protein levels of CYP3A11/3A4 in mouse liver tissue and human HepG2 cells. The reporter gene-transfected cells were used to identify upstream targets in HepG2 cells. RESULTS: LPS injection in mice resulted in the up-regulation of pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in liver, up-regulation of hepatic enzymes such as Tbil, ALT, AST and ALP in serum, and down-regulation of CYP3A11/3A4 expression in liver. Ginsenosides treatment reversed the up-regulation of pro-inflammatory cytokines and serum hepatic enzymes elicited by LPS. Pathological results suggest that ginsenosides reduced liver damage. Moreover, ginsenosides reversed the decrease of CYP3A11/3A4 expression in the liver of LPS-injured mouse and in LPS-treated HepG2 cells. To further investigate the regulatory mechanisms, we found that ginsenosides enhanced the rifampicin-induced pregnane X receptor (PXR) transactivation of the CYP3A4 promoter. Treatment of hPXR-over-expressed cells with ginsenosides increased the rifampicin-inducible expression of CYP3A4 in a concentration-dependent manner. CONCLUSION: Ginsenosides reverse the effects of LPS-induced hepatic CYP3A11/3A4 dysfunction, suggesting that the stabilization of the CYP3A11/3A4 expression in an injured liver appears a novel hepatoprotective mechanism of ginsenosides.