Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species.

The aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.

Ultrasonic-assisted activated carbon separation removing bacterial endotoxin from salvia miltiorrhizae injection.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Echinocystic acid prevents obesity and fatty liver via interacting with FABP1.

Long-term high-fat diet (HFD) will lead to obesity and their complications. Echinocystic acid (EA), a triterpene, shows anti-inflammatory and antioxidant effects. We predict that EA supplementation can prevent obesity, diabetes, and nonalcoholic steatohepatitis. To test our hypothesis, we investigated the effects of EA supplementation on mice with HFD-induced obesity in vivo and in vitro by adding EA to the diet of mice and the medium of HepG2 cells, the protein target of EA was analyzed by molecular docking. The results showed that EA ameliorated obesity and inhibited blood triglyceride and liver triglyceride concentrations than those in the HFD groups. The data on molecular docking indicated that FABP1 was a potential target of EA. Further experimental results confirmed that EA affected the triglyceride level by regulating the function of FABP1. This study may provide a new potential inhibitor for FABP1 and a new strategy for the treatment of obesity.

Purple Rehmannia: Investigation of the activation of R2R3-MYB transcription factors involved in anthocyanin biosynthesis.

Engineering anthocyanin biosynthesis in herbs could provide health-promoting foods for improving human health. Rehmannia glutinosa is a popular medicinal herb in Asia, and was a health food for the emperors of the Han Dynasty (59 B.C.). In this study, we revealed the differences in anthocyanin composition and content between three Rehmannia species. On the 250, 235 and 206 identified MYBs in the respective species, six could regulate anthocyanin biosynthesis by activating the ANTHOCYANIDIN SYNTHASE (ANS) gene expression. Permanent overexpression of the Rehmannia MYB genes in tobacco strongly promoted anthocyanin content and expression levels of NtANS and other genes. A red appearance of leaves and tuberous/roots was observed, and the total anthocyanin content and the cyanidin-3-O-glucoside content were significantly higher in the lines overexpressing RgMYB41, RgMYB42, and RgMYB43 from R. glutinosa, as well as RcMYB1 and RcMYB3 in R. chingii and RhMYB1 from R. henryi plants. Knocking out of RcMYB3 by CRISPR/Cas9 gene editing resulted in the discoloration of the R. chingii corolla lobes, and decreased the content of anthocyanin. R. glutinosa overexpressing RcMYB3 displayed a distinct purple color in the whole plants, and the antioxidant activity of the transgenic plants was significantly enhanced compared to WT. These results indicate that Rehmannia MYBs can be used to engineer anthocyanin biosynthesis in herbs to improve their additional value, such as increased antioxidant contents.

Chaihu-Guizhi-Ganjiang Decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis.

BACKGROUND: Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment remains elusive. METHODS: Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. The efficacy and changes of metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis was performed. RESULTS: Efficacy was measured according to the Rome IV criteria and TCM theory. Our results indicated that CGGD showed significantly better efficacy than Dicetel in the treatment of IBS utilizing each criterion. CGGD exerted greater effects on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD treatment significantly (p < 0.05) increased carnitine metabolism, with elevated levels of L-carnitine and acylcarnitine in plasma. Such changes in these metabolites could exert effects against IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation. CONCLUSIONS: CGGD appeared to be more efficacious than Dicetel for treating patients with IBS. The findings provide a sound support for the underlying biomolecular mechanism of CGGD in the prevention and treatment of IBS.

Elucidating the particle size effect of andrographolide suspensions on their IVIVC performance in oral absorption.

The study aimed to explore the size effect on the in vitro-in vivo correlation (IVIVC) in the oral absorption of andrographolide nanosuspensions (Ag-NS). Ag-NS with controllable particle sizes were prepared by ultrasonic dispersion method, and the formulation and process parameters were optimized through single factor experiments using mean particle size, polydispersity index, and stability as evaluation indicators. The morphology of Ag-NS was observed by scanning electron microscopy (SEM), and the crystalline state of the nanosuspensions was characterized by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The dissolution tests were carried out with the paddle method in two different mediums simulating the pH conditions in intestinal fluid (pH 6.8) and gastric fluid (pH 1.2), respectively. The pharmacokinetic behaviors were investigated in rats after oral administration, and a deconvolution approach was introduced to determine the correlation between in vitro dissolution and in vivo absorption (IVIVC). The formulation with the use of lecithin and PEG-800 as stabilizers showed its potential in the size-controllable preparation of Ag-NS. Via altering the ultrasonication amplitude and time, three Ag-NS suspensions with three particle sizes, i.e., Ag-NS 250 (249.8 ± 1.3 nm), Ag-NS 450 (485.2 ± 3.7 nm), Ag-NS 1000 (1015 ± 36.1 nm) were prepared. Their morphological and crystal characteristics were not changed during the size reduction process, but both of their in vitro dissolution and in vivo absorption were improved. Relatively better IVIVC performance was observed with the in vitro dissolution data at pH 6.8 (r > 0.9). With the reduction of particle size, the in vivo absorption fraction was more closed to the level of the in vitro dissolution. In conclusion, the decrease in particle size would improve the dissolution and absorption of Ag-NS, and also affect their IVIVC performance. The study would facilitate the design and quality control of Ag-NS in terms of particle size and dissolution specifications.

Milk and Egg Are Risk Factors for Adverse Effects of Capecitabine-Based Chemotherapy in Chinese Colorectal Cancer Patients.

BACKGROUND: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. METHODS: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. RESULTS: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. CONCLUSIONS: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03030508.

Choline deficiency-related multi-omics characteristics are susceptible factors for chemotherapy-induced thrombocytopenia.

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Differentially expressed features (DEFs) from each uni-omics analysis were then subjected to integrative analysis using Multi-Omics Factor Analysis (MOFA). Choline-deficiency in plasma and CRT was found as the most critical TCP-related feature. Based on bioinformatic analysis and literature research, we further concluded that choline-deficiency was the possible reason for most of the other TCP-related multi-omics DEFs, including metabolites representing reduced sphingolipid de novo synthesis and elevated solute carrier-mediated transmembrane transportation in CRT and plasma, DNA hypermethylation and elevated expression of genes involved in neuronal system genes. In terms of thrombocytopoiesis, these TCP-related DEFs may cause atypical maintenance and differentiation of megakaryocyte, resulting a suppressed ability of thrombocytopoiesis, making patients more susceptible to chemotherapy-induced TCP. At last, prediction models were developed and validated with reasonably good discrimination. The area under curves (AUCs) of training sets were all > 0.9, while validation sets had AUCs between 0.778 and 0.926. In conclusion, our results produced reliable marker systems for predicting TCP and promising target for developing precision treatment to prevent TCP.

Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers.

Wuzhi capsule (WZC), a preparation of Fructus Schisandra sphenanthera extract, has been used widely for the treatment of viral and drug-induced hepatitis in China. This study aimed to determine the pharmacokinetic parameters of tacrolimus (TAC) when co-administered with WZC and the dose-effect of WZC on tacrolimus in healthy volunteers. The effect of an increased dosage of WZC (1, 2, 6, and 8 capsules once daily) on the relative oral exposure of tacrolimus was assessed to explore the dose-response relationship between WZC and tacrolimus using bioanalysis, pharmacokinetic, and genotypical analyses. The influence of CYP3A5 and MDR1 genetic polymorphisms on the WZC dose was elucidated by maintaining the Ctrough of tacrolimus in Chinese healthy volunteers. When co-administered with WZC, the Tmax of tacrolimus was increased significantly while the apparent oral clearance was decreased. The plasma tacrolimus level in volunteers with high CYP3A5 expression was much lower than that in those with mutant CYP3A5. However, polymorphisms of MDR1 exon26 C3435T, exon21 G2677T/A, and exon12 C1236T were not associated with plasma tacrolimus levels. Our findings provide important information on interactions between modern medications and herbal products, thus facilitating a better usage of tacrolimus in patients receiving WZC.

Biosynthesis-based spatial metabolome of Salvia miltiorrhiza Bunge by combining metabolomics approaches with mass spectrometry-imaging.

Defining the spatial distributions of metabolites and their structures are the two key aspects for interpreting the complexities of biosynthesis pathways in plants. As a means of obtaining information on the spatial distribution of metabolites, a strategy is needed that has high sensitivity and allows visualization. Toward this goal, we carried an untargeted metabolomics to obtain detailed metabolic information on different plant parts of Salvia miltiorrhiza, the roots of which are widely used in traditional Chinese medicine. Systematic optimization of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) including parameter selection and sample preparation were carried out to improve the sensitivity of the method for plant samples. Guided by the metabolomics data, the spatial distributions of diverse metabolites, including phenolic acids, flavonoids, tanshinones, carbohydrates, and lipids, were characterized and visualized for both the underground and aerial parts. To integrate the information pertaining to the spatial distribution of metabolites, the flavonoids and phenolic acids (phenylpropanoid metabolic pathway) were chosen as examples for in-depth study the biosynthesis pathways in S. miltiorrhiza. The complementary data obtained from the metabolomics study and mass spectrometry imaging enabled the identification of key reactions involved in flavonoid biosynthesis in flowers, which lead the changes in metabolite distribution. The analysis also identified the core precursor for phenolic acid biosynthesis in Salvia species. Therefore, the powerful combination of metabolomics and mass spectrometry imaging provides a basis for obtaining detailed information on spatial metabolome and constitutes a platform for deep understanding the biosynthesis of bioactive metabolites in plants.

[Effects of density on growth and gene transcription characteristics of Rehmannia glutinosa].

The present study analyzed the effects of planting density on the development, quality, and gene transcription characte-ristics of Rehmannia glutinosa using 85-5 and J9 as materials with three planting densities of 5 000, 25 000, and 50 000 plants/Mu(1 Mu≈667 m~2). The agronomic characteristics of leaves and tuberous roots, the content of catalpol and acteoside, and the changes of gene expression were determined. The results showed that the leaf size, the diameter of tuberous root, leaf biomass, tuberous root number, and tuberous root biomass per plant at low density were significantly higher than those of medium and high densities. The content of catalpol and acteoside in leaves was higher at high density. The content of catalpol in tuberous roots was higher at low density, and the change trend was similar to that in leaves, while the content of acteoside in tuberous roots was higher at high density. Transcriptome analysis found that about 1/2 of the expansin genes could change regularly in response to density treatment, which was rela-ted to the development of tuberous roots. The change trend of the gene expression of multiple catalytic enzymes involved in the biosynthesis of catalpol and acteoside was consistent with that of their content, which was presumedly involved in the accumulation and regulation of density-responsive medicinal components. Based on the analysis of the development, medicinal components, and gene expression characteristics of R. glutinosa at different densities, this study is expected to provide an important basis for regulating the quality and yield of medicinal materials of R. glutinosa by managing the planting density.

Efficient CRISPR/Cas9-mediated genome editing in Rehmannia glutinosa.

KEY MESSAGE: Here, we cloned a phytoene desaturase (PDS) gene from Rehmannia glutinosa, and realized RgPDS1 knock out in R. glutinosa resulted in the generation of albino plants. Rehmannia glutinosa is a highly important traditional Chinese medicine (TCM) with specific pharmacology and economic value. R. glutinosa is a tetraploid plant, to date, no report has been published on gene editing of R. glutinosa. In this study, we combined the transcriptome database of R. glutinosa and the reported phytoene desaturase (PDS) gene sequences to obtain the PDS gene of R. glutinosa. Then, the PDS gene was used as a marker gene to verify the applicability and gene editing efficiency of the CRISPR/Cas9 system in R. glutinosa. The constructed CRISPR/Cas9 system was mediated by Agrobacterium to genetically transform into R. glutinosa, and successfully regenerated fully albino and chimeric albino plants. The next-generation sequencing (NGS) confirmed that the albino phenotype was indeed caused by RgPDS gene target site editing, and it was found that base deletion was more common than insertion or replacement. Our results revealed that zCas9 has a high editing efficiency on the R. glutinosa genome. This research lays a foundation for further use of gene editing technology to study the molecular functions of genes, create excellent germplasm, accelerate domestication, and improve the yield and quality of R. glutinosa.

Extraction optimization, physicochemical properties and antioxidant and hypoglycemic activities of polysaccharides from roxburgh rose (Rosa roxburghii Tratt.) leaves.

The optimum extraction conditions of polysaccharides from roxburgh rose (Rosa roxburghii Tratt.) leaves (RLP) were obtained by response surface methodology (RSM), which were a liquid to solid ratio of 21.16 mL/g, an extraction temperature of 81.32 °C, and an extraction time of 90.49 min. An RLP yield of 11.04% was obtained under these conditions. DEAE-52 cellulose and Sepharose CL-6B columns were used to purify the RLP, and the purified polysaccharide components RLP-1.2 and RLP-2.1 were obtained. Both RLP-1.2 and RLP-2.1 were composed of galacturonic acid (GalA), glucose (Glc), galactose (Gal), and arabinose (Ara). However, the molar ratios of GalA, Glc, Gal, and Ara in RLP-1.2 and RLP-2.1 were different. At a concentration of 10 mg/mL, the α-amylase inhibitory activities of RLP-1.2 and RLP-2.1 reached 80.74% and 89.85% that of acarbose, respectively, and the α-glucosidase inhibitory activity of RLP-1.2 reached 87.91% that of acarbose. In addition, both RLP-1.2 and RLP-2.1 showed good antioxidant activity. These results suggested that RLP-1.2 and RLP-2.1 possess potential as natural hypoglycemic agents or natural antioxidants.

Comparison of oral health behaviour between dental and non-dental undergraduates in a university in southwestern China--exploring the future priority for oral health education.

BACKGROUND: Based on a national survey in 2015, people's oral health behaviour (OHB) has not kept up with the pace of knowledge and attitudes in China after decades of oral health education (OHE). Thus, we need to improve OHE to strengthen people's OHB. Undergraduates are regarded as the best candidates for the improvement of OHE. The objective of this study is to determine undergraduates' oral health status and existing problems in OHB by comparing dental and non-dental students at Sichuan University. We hope to provide some suggestions for future OHE to improve people's OHB. METHODS: A quasi-experimental study designed with a pre-test and post-test group was conducted. A total of 217 dental students and 135 non-dental students were enrolled. They were administered an OHE course focused on OHB. A survey about oral health behaviour and knowledge was conducted before and after the course. RESULTS: According to the pre-course survey, dental students surpassed non-dental students in terms of toothbrushing frequency, method, and time, but unfortunately, flossing was overlooked by all the students. After the course, both dental and non-dental students showed strong willingness to improve their OHB. More non-dental students than dental students were willing to use toothpicks and Chinese herbal toothpaste before and after the course. CONCLUSIONS: OHE focused on behaviour has a positive effect on university students. Future OHE and interventions should focus on flossing, toothbrushing methods, toothpicks, Chinese herbal toothpaste and modifications to adopt new media.

Low-dose photodynamic therapy-induced increase in the metastatic potential of pancreatic tumor cells and its blockade by simvastatin.

Pancreatic tumor are a deadly malignancy with high aggressiveness, and photodynamic therapy (PDT) is a prospective remedy. Nevertheless, the cells in the peripheral tissues of large tumors are often subjected to low-dose illumination and tend to survive after sublethal PDT exposure. Thus, it is of critical importance to determine the metastatic influence of PDT on pancreatic neoplasms. (17R, 18R)-2-(1-Hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1) is a novel chlorine derivative photosensitizer, and we previously demonstrated potent growth inhibition of pancreatic neoplasms by YLG-1-mediated PDT (YLG-1-PDT). In this study, we assessed the metastatic effect of low-dose PDT with YLG-1 on pancreatic tumors and its combination with simvastatin. We found that sublethal YLG-1-PDT promoted MMP-2/9 expression in residual pancreatic tumor cells as well as tumor cell motility/invasion and liver metastasis. Since simvastatin was reported to improve the survival of patients with pancreatic tumors at an early stage and suppress the metastasis of most cancers, we utilized it during YLG-1-PDT and discovered alleviated migration/invasion, metastasis and MMP-2/9 expression. Collectively, our study results raise the concern that PDT could also be a Janus-like treatment owing to its prometastatic potential provoked by a low dosage. Concomitant use of simvastatin during PDT might be an effective method to attenuate such adverse reactions.

Multiple reversible encephalitic attacks: a rare manifestation of neuronal intranuclear inclusion disease.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative condition characterized by the loss of neurons and the presence of eosinophilic nuclear inclusions in the central and peripheral nervous system, skin and visceral organs. In this paper, we present a case of NIID with recurrent encephalitic attacks that remained stable and nonprogressive for seven years; no such case has previously been reported. CASE PRESENTATION: A 63-year-old female was hospitalized due to light-headedness, vomiting, unstable gait and cognitive impairment. Seven years prior, she had experienced an episode of light-headedness, central facial paralysis, unstable gait, aphasia, nausea, vomiting and loss of consciousness. She regained consciousness within 12 h, and her other symptoms were completely resolved within one week. During the present hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity on diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. We reviewed the patient's previous MRI results and found that she had also had high signal intensity on DWI of the bilateral frontal grey matter-white matter junction seven years prior. In the intervening seven years, the high signal intensity in the frontal lobes had spread along the grey matter-white matter junction, but the deep white matter remained unaffected. Skin biopsy was performed, and intranuclear inclusions were found in adipocytes, fibroblasts and sweat gland cells. GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID. She received supportive treatment such as nutrition support therapy and vitamin B and C supplementation, as well as symptomatic treatment during hospitalization. The patient's symptoms were completely relieved within one week. CONCLUSION: This is a detailed report of a case of NIID with multiple reversible encephalitic attacks, diagnosed by clinical symptoms, intranuclear inclusions, characteristic DWI signals, and genetic tests.

Polysaccharide from Angelica Sinensis Suppresses Inflammation and Reverses Anemia in Complete Freund's Adjuvant-induced Rats.

The anti-inflammatory and antianemic activities of Angelica sinensis polysaccharide (ASP) isolated from roots of Angelica sinensis (AS) was investigated in a complete Freund's adjuvant (CFA)-induced arthritic rat model. It was observed that serum iron (SI) and total iron binding capacity (TIBC) levels were elevated after 4-week oral administration of ASP. Red blood cell (RBC) count and hemoglobin (Hb) concentrations were ameliorated as well. Moreover, inflammatory cytokines IL-6 and TNF-a were decreased strikingly in CFA-induced arthritic rats after treatment of ASP. Evidence also showed that ASP strongly inhibited hepcidin expression through the Janus kinase/signal transducers and activators of transcription (JAK2/STAT3) pathway. Furthermore, ASP exhibited reduced primary and secondary lesions in adjuvant arthritis, attenuating synovitis and inflammatory joint damage. Data presented in this article collectively indicated that ASP significantly decreased proinflammatory cytokines (TNF-a, IL-6), which might play a crucial role in the CFA-induced arthritic rats, and had a therapeutic effect on adjuvant arthritis in rats. Results of Western blot analysis indicated that ASP inhibited the activation of IL-6/JAK2/STAT3 signaling pathway in the CFA-induced arthritic rats.

A review of the ethnopharmacology, phytochemistry, pharmacology, and quality control of Scutellaria barbata D. Don.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata D. Don (S. barbata) is a well-known perennial herb that is used in traditional Chinese and Korean medicine. In China, it is known as Ban Zhi Lian, while in Korea, it is known as Banjiryun. In the Traditional Chinese Medicine (TCM) system, S. barbata has heat-clearing and detoxifying properties (Qingre Jiedu in Chinese). AIM OF THE REVIEW: To provide a systematic review on current multifaceted understanding of S. barbata, with particular emphasis on the correlation between its traditional applications and pharmacological activities. MATERIALS AND METHODS: All available S. barbata-related information from internet databases, including PubMed, Science Direct, Elsevier, China National Knowledge Internet, and Google Scholar (up to October 2018) were searched. Additional information was gathered from classical books on Chinese Herbals, Chinese Pharmacopoeia, and so on. RESULTS: In the TCM system, S. barbata is mainly prescribed for its heat-clearing and detoxifying effects. More than 203 compounds have been isolated and identified from this herb, with neo-clerodane diterpenoids and flavonoids as the main compounds. Most neo-clerodanes have been demonstrated to have cytotoxic effects against different cancer cell types in vitro. The S. barbata extracts exhibited anti-inflammatory, anti-microbial, antitumor, and other pharmacological activities. To add, flavonoids, including wogonin, baicalein, apigenin, naringenin, and scutellarin, were identified as the key to quality control. CONCLUSIONS: The heat-clearing effects of S. barbata could be attributed to its anti-inflammatory and hepatoprotective activities, whereas its detoxifying effects might be due to the anti-microbial functions of neo-clerodane diterpenoids and flavones. S. barbata may display anti-tumor effects and through active ingredient analysis, neo-clerodane diterpenoids are suggested to be its representative compounds. Overall, many pre-clinical studies have been conducted but very little concrete evidences are available on its specific effects, which are of therapeutic relevance.

A randomized controlled trial of mindfulness-based stress reduction for insomnia secondary to cervical cancer: Sleep effects.

AIM: To evaluate the efficacy of mindfulness-based stress reduction on objective and subjective sleep parameters and hypnotic medication use of patients with insomnia secondary to cervical cancer. METHODS: This was a randomized controlled trial enrolled insomnia patient who were caused or worsened by cervical cancer. Seventy patients with insomnia caused or aggravated by cervical cancer were at random divided into either a usual care group or an 8-week mindfulness-based stress reduction group. Subjective sleep parameters, objective sleep parameters and hypnotic medication consumption were assessed at baseline, after the program, 6- and 12-month after finishing the interventions. RESULTS: The results showed that mindfulness-based stress reduction had a positive effect on subjective sleep parameters (Total wake time: ∆ = 45.32, P < 0.05; Sleep efficacy: ∆ = 6.87, P < 0.05; Total sleep time: ∆ = 22.22, P < 0.01). Compared with control group, polysomnography data in mindfulness-based stress reduction group were not improved significantly. There were no associations between subjective sleep parameters and objective sleep parameters. CONCLUSION: Mindfulness-based stress reduction had a definite impact on patients with insomnia that was secondary to cervical cancer just after the intervention, but no long-term influences. TRIAL REGISTRATION: ChiCTR1800018571; 9/25/2018; retrospectively registered.