Determination of α-Dicarbonyl compounds in traditional Chinese herbal medicines.

α-DCs (α-dicarbonyls) have been proven to be closely related to aging and the onset and development of many chronic diseases. The wide presence of this kind of components in various foods and beverages has been unambiguously determined, but their occurrence in various phytomedicines remains in obscurity. In this study, we established and evaluated an HPLC-UV method and used it to measure the contents of four α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) in 35 Chinese herbs after they have been derivatized with 4-nitro-1,2-phenylenediamine. The results uncover that 3-DG is the major component among the α-DCs, being detectable in all the selected herbs in concentrations ranging from 22.80 µg/g in the seeds of Alpinia katsumadai to 7032.75 µg/g in the fruit of Siraitia grosuenorii. The contents of the other three compounds are much lower than those of 3-DG, with GO being up to 22.65 µg/g, MGO being up to 55.50 µg/g, and DA to 18.75 µg/g, respectively. The data show as well the contents of the total four α-DCs in the herbs are generally in a comparable level to those in various foods, implying that herb medicines may have potential risks on human heath in view of the α-DCs.

Genome-wide identification of the alkaloid synthesis gene family CYP450, gives new insights into alkaloid resource utilization in medicinal Dendrobium.

The medicinal Dendrobium species of Orchidaceae possess significant pharmaceutical value, and modern pharmacological research has shown that Dendrobium contains many important active ingredients. Alkaloids, the crucial components of medicinal Dendrobium, demonstrate beneficial healing properties in cardiovascular, cataract, gastrointestinal, and respiratory diseases. Members of the cytochrome P450 monooxygenase (CYP) gene family play essential roles in alkaloid synthesis, participating in alkaloid terpene skeleton construction and subsequent modifications. Although studies of the CYP family have been conducted in some species, genome-wide characterization and systematic analysis of the CYP family in medicinal Dendrobium remain underexplored. In this study, we identified CYP gene family members in the genomes of four medicinal Dendrobium species recorded in the Pharmacopoeia: D. nobile, D. chrysotoxum, D. catenatum, and D. huoshanense. Further, we analyzed the motif composition, gene replication events, and selection pressure of this family. Syntenic analysis revealed that members of the clan 710 were present on chromosome 18 in three medicinal Dendrobium species, except for D. nobile, indicating a loss of clan 710 occurring in D. nobile. We also conducted an initial screening of the CYP genes involved in alkaloid synthesis through transcriptome sequencing. Quantitative real-time reverse transcription PCR showed that the expression of DnoNew43 and DnoNew50, homologs of secologanin synthase involved in the alkaloid synthesis pathway, was significantly higher in the stems than in the leaves. This result coincided with the distribution of dendrobine content in Dendrobium stems and leaves, indicating that these two genes might be involved in the dendrobine synthesis pathway. Our results give insights into the CYP gene family evolution analysis in four medicinal Dendrobium species for the first time and identify two related genes that may be involved in alkaloid synthesis, providing a valuable resource for further investigations into alkaloid synthesis pathway in Dendrobium and other medicinal plants.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

[Determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis by gel permeation chromatography-gas chromatography-ion trap mass spectrometry].

With the growing global popularity of traditional medicine and natural drugs， especially in Southeast Asia， the quality of traditional Chinese medicines （TCMs） has attracted the attention of regulators. China's major TCM export destinations， such as South Korea， Japan， and Europe， have formulated strict maximum residue limits （MRLs） of pesticides in TCMs. Therefore， a sensitive and high-throughput method for the simultaneous determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis was established， involving gel permeation chromatography （GPC） coupled with gas chromatography-ion trap mass spectrometry （GC-ITMS）. In this method， the samples were first ground into fine powder and extracted twice with 20 mL acetonitrile in an ultrasonic cleaner for 30 min. After centrifugation for 10 min at 6000 r/min， the supernatants were combined and dried at 40 ℃ using a rotary vacuum evaporator. The residue was re-dissolved in 2 mL ethyl acetate-cyclohexane （1∶1， v/v） and purified by gel permeation chromatography using a 40 cm×20 mm column. The eluent collecting time was optimized as 17-30 min to ensure both the recovery of target compounds and the removal of interferences such as pigments and lipids from the target compounds. The eluent was then dried and re-dissolved with 1 mL toluene for analysis. The 101 pesticide residues were separated using the DB-5MS capillary column and analyzed by ion trap mass spectrometry. The pretreatment conditions and ion trap mass spectrometry parameters were optimized to effectively reduce the interference of complex TCM matrices and greatly improve the quantitative accuracy of the analysis and recovery of the target pesticides. Three spiked levels of 101 pesticides were tested. The average recovery range was 58.3%-108.9% and the relative standard deviations （RSDs） at the three spiked levels （n=10） ranged from 0.4% to 16.5%. The limits of detection （LODs， S/N=3） of the 101 pesticide compounds ranged from 0.2 to 40.0 µg/kg， while the limits of quantification （LOQs， S/N=10） ranged from 0.6 to 120.0 µg/kg， which met the maximum residue limits of China's main TCM export countries and organizations. This rapid analysis method was easy to operate and high throughput， with strong sensitivity and good repeatability. The employment of gel permeation chromatography overcame the drawback of inadequate cleanup of the solid phase extraction column during TCM analysis. The application of ion trap technology further eliminated the interference of matrix impurities and increased the accuracy of the quantitative and qualitative analyses. This method fills the knowledge gap in multiple pesticide residue determination in TCMs using gas chromatography-ion trap mass spectrometry and is a useful and beneficial alternative to current analytical methods of TCMs.

Effects of Elephantopus scaber extract on growth, proximate composition, immunity, intestinal microbiota and resistance of the GIFT strain of Nile tilapia Oreochromis niloticus to Streptococcus agalactiae.

This study aimed to investigate the effects of Elephantopus scaber extract on the GIFT (genetic improvement of farmed tilapia) strain of Nile tilapia Oreochromis niloticus. A total of 800 tilapia with an initial body weight of 1.34 ± 0.09 g each were randomly divided into five groups. The tilapia in the control group (E0 group) were fed on a basal diet only. Meanwhile, tilapia in the four experimental groups were fed on a basal diet supplemented with 1 g/kg (E1 group), 3 g/kg (E2 group), 5 g/kg (E3 group), and 7 g/kg (E4 group) of E. scaber extract for 10 weeks. Results showed that the survival rate was higher in the experimental groups than in the control group. Compared with the control group, some growth parameters (FW, WGR, SGR, VSI, and HSI) were significantly improved in the E1 group and E2 group. The crude lipid content in the dorsal muscle and liver was lower in the E1 group than in the control group. After E. scaber extract supplementation, activities of immunity-related enzymes (ACP, AKP, T-AOC, SOD, CAT, GSH-Px and LZM) in plasma, liver, spleen and head kidney, and expressions of immunity-related genes (IL-1ß, IFN-γ, TNF-α, and CCL-3) in liver, spleen and head kidney showed various degrees of improvement, while MDA content and Hsp70 expression level were decreased. The survival rate of tilapia increased in all the supplementation groups after Streptococcus agalactiae treatment. E. scaber extract addition changed the species composition, abundance, and diversity of intestinal microbiota in tilapia. These results demonstrate that E. scaber extract supplementation in diet can improve the growth, immunity, and disease resistance of GIFT against S. agalactiae. E. scaber extract supplementation can also change intestinal microbiota and reduce crude lipid content in dorsal muscle and liver. The above indicators show that the optimal dose of E. scaber extract for GIFT is 1 g/kg.

Comparative Analysis of the Efficacy of Transurethral Bipolar Plasma Needle Electrode and Ring Electrode in the Treatment of Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the most prevalent tumor of the urinary tract, ranking seventh in males and seventeenth in women. The gold standard for the definitive diagnosis and initial treatment of non-muscle-invasive bladder cancer is transurethral resection (TUR) of the bladder tumor. The ability to accurately detect disease, typically in the presence of hematuria as well as to detect early recurrent tumors in patients with a history of NMIBC, is critical to the successful treatment of non-muscle-invasive bladder cancer (NMIBC). Unfortunately, the current biomarker landscape for NMIBC is still evolving. Cystoscopy remains the gold standard, but it can still miss 10% of tumors. As a result, physicians frequently employ additional diagnostic tools to aid in the diagnosis of bladder cancer. The efficacy of transurethral bipolar plasma needle electrodes and ring electrodes in the treatment of non-muscle-invasive bladder cancer was compared and analyzed in this study. During our study, 100 patients with non-muscle-invasive bladder cancer admitted to our hospital between June 2019 and June 2020 were randomly assigned to a control group and an observation group, with 50 cases in each group. The observation group was given a bipolar plasma needle electrode, while the control group was given a bipolar plasma ring. Patients continued to receive bladder irrigation chemotherapy as well as traditional Chinese medicine (TCM) treatment as part of our treatment plan, while the control group received only bladder irrigation chemotherapy. Clinical factors such as operational blood loss, catheter indention time, length of hospital stay, and others were compared between the two groups. When the risk grades in the two groups were compared, the observation group had fewer medium- and high-risk grades than the control group, but the control group had more low-risk grades, with statistical significance (P < 0.05).

Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

Effects of dietary trehalose on growth, trehalose content, non-specific immunity, gene expression and desiccation resistance of juvenile red claw crayfish (Cherax quadricarinatus).

This study was performed to investigate the effects of dietary trehalose on growth, muscle composition, non-specific immune responses, gene expression and desiccation resistance of juvenile red claw crayfish (Cherax quadricarinatus). A total of 540 (body weight of 0.41 ± 0.05) crayfish were randomly divided into six groups for a feeding experiment. Six diets with trehalose levels at 0 (Diet 1), 1 (Diet 2), 2 (Diet 3), 5 (Diet 4), 10 (Diet 5) and 15 (Diet 6) g kg-1 were prepared to feed juvenile red claw crayfish for 8 weeks. The results showed that the weight gain rate (WGR) and specific growth rate (SGR) of crayfish in Diet 4, Diet 5 and Diet 6 groups were significantly improved compared with the control group (Diet 1). Muscle crude protein contents of crayfish fed Diet 4, Diet 5 and Diet 6 were significantly higher than those of the control group. The activities of superoxide dismutase (SOD) and alkaline phosphatase (AKP) in hepatopancreas and hemolymph of crayfish for Diet 4, Diet 5, and Diet 6 groups were significantly increased while malondialdehyde (MDA) content was significantly reduced when compared with the control. The total antioxidant capacity (T-AOC), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatopancreas and hemolymph of crayfish fed Diet 5 and Diet 6 were significantly higher than those in the control group. However, acid phosphatase (ACP) activity was not significantly different among all experimental groups. The hepatopancreas and intestine trehalose contents of crayfish showed an upward trend with the increase of dietary trehalose levels. Compared with the control group, supplementation of 5-15 g kg-1 trehalose in the feed up-regulated the expression levels of GPx, C-type lysozyme (C-LZM), antilipolysacchride factor (ALF), facilitated trehalose transporter homolog isoform X2 (Tret1-2) and facilitated trehalose transporter isoform X4 (Tret1-4) mRNA. In addition, supplementation of 5-15 g kg-1 trehalose in the feed could improve the survival rate of red claw crayfish under desiccation stress. These results suggested that supplementation of 5-15 g kg-1 trehalose in feed could significantly improve the growth performance, muscle protein, non-specific immunity and desiccation resistance of juvenile red claw crayfish.

Efficacy of the combination of modern medicine and traditional Chinese medicine in pulmonary fibrosis arising as a sequelae in convalescent COVID-19 patients: a randomized multicenter trial.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. METHODS: Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. DISCUSSION: Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. TRIAL REGISTRATION: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).

Corrigendum to "Yiqi Huayu Jiedu Decoction Inhibits the Invasion and Metastasis of Gastric Cancer Cells through TGF-ß/Smad Pathway".

[This corrects the article DOI: 10.1155/2017/1871298.].

New malonylginsenosides from the fresh fruits of Panax notoginseng.

Four new malonylginsenosides, malonylnotoginsenoside Fe (1), malonylnotoginsenoside Ra1 (2), malonylgypenoside LXXV (3), and malonylginsenoside Mc (4), together with two known analogues, malonylfloralginsenoside Rc1 (5) and malonylginsenoside Rc (6), were isolated from the fresh fruits of Panax notoginseng. Their structures were determined by MS and NMR experiments. The anti-proliferative activities of the malonylginsenosides (1-6) against SH-SY5Y human neuroblastoma cell line were evaluated using the MTT assay.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen.

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.

Autophagy activation by Jiang Zhi Granule protects against metabolic stress-induced hepatocyte injury.

AIM: To elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury. METHODS: An in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 µg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62. Western blot analyses were performed to examine the expression of LC3-II/LC3-I, p62, mTOR and PI3K, while mitochondrial integrity and oxidative stress were observed by fluorescence staining of JC-1 and reactive oxygen species. C57BL/6 mice were divided into three groups: control group (n = 10), high fat (HF) group (n = 13) and JZG group (n = 13); and, histological staining was carried out to detect inflammation and lipid content in the liver. RESULTS: The cell trauma induced by PA was aggravated in a dose- and time-dependent manner, and hepatic function was improved by JZG. PA had dual effects on autophagy by activating autophagy induction and blocking autophagic flux. The PI3K-AKT-mTOR signaling pathway and the fusion of isolated hepatic autophagosomes and lysosomes were critically involved in this process. JZG activated autophagy progression by either induction of autophagosomes or co-localization of autophagosomes and lysosomes as well as degradation of autolysosomes to protect against PA-induced hepatocyte injury, and protected mitochondrial integrity against oxidative stress in PA-induced mitochondrial dysfunction. In addition, JZG ameliorated lipid droplets and inflammation induced by HF diet in vivo, leading to improved metabolic disorder and associated liver injury in a mouse model of non-alcoholic fatty liver disease (NAFLD). CONCLUSION: Metabolic stress-induced hepatocyte injury exhibited dual effects on autophagy and JZG activated the entire process, resulting in beneficial effects in NAFLD.

Yiqi Huayu Jiedu Decoction Inhibits the Invasion and Metastasis of Gastric Cancer Cells through TGF-ß/Smad Pathway.

Background. Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival. Methods. In vitro experiments, we observe YHJD's effect on the cells' proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells' adhesion, migration, and invasion, respectively. Inhibitor (10 µM/L of SB431542) and activator (10 ng/mL of TGF-ß) of TGF-ß/Smad pathway were used to estimate whether YHJD's impact on the biological behavior of gastric cancer cells was related to TGF-ß/Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF-ß/Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice. Results. YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF-ß, Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF-ßR I, p-Smad2, p-Smad3, Snail, and Slug reduced. Conclusion. YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF-ß/Smad pathway.

Effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after oral administration.

BACKGROUND: Both ginsenoside Re and B-complex vitamins are widely used as nutritional supplements. They are often taken together so as to fully utilize their antifatigue and refreshing effects, respectively. Whether actually a drug-nutrient interaction exists between ginsenoside Re and B-complex vitamins is still unknown. The objective of this study was to simultaneously investigate the effect of B-complex vitamins on the antifatigue activity and bioavailability of ginsenoside Re after their oral administration. The study results will provide valuable theoretical guidance for the combined utilization of ginseng and B-complex vitamins. METHODS: Ginsenoside Re with or without B-complex vitamins was orally administered to mice to evaluate its antifatigue effects and to rats to evaluate its bioavailability. The antifatigue activity was evaluated by the weight-loaded swimming test and biochemical parameters, including hepatic glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of ginsenoside Re in plasma was determined by liquid chromatography-tandem mass spectrometry. RESULTS: No antifatigue effect of ginsenoside Re was noted when ginsenoside Re in combination with B-complex vitamins was orally administered to mice. B-complex vitamins caused to a reduction in the bioavailability of ginsenoside Re with the area under the concentration-time curve from zero to infinity markedly decreasing from 11,830.85 ± 2,366.47 h·ng/mL to 890.55 ± 372.94 h·ng/mL. CONCLUSION: The results suggested that there were pharmacokinetic and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B-complex vitamins. B-complex vitamins can significantly weaken the antifatigue effect and decrease the bioavailability of ginsenoside Re when simultaneously administered orally.

Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy.

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. METHODS: A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were used to evaluate the therapeutic efficacy before transplantation and 3, 6, and 12 months after transplantation. RESULTS: Three months after cell transplantation, scores in the A dimension of GMFM and the A and C dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). Six months after cell transplantation, scores in the A, B dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are higher than those of the BMMNC and the control groups (P < 0.05). Twelve months after cell transplantation, scores in the A, B, and C dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). No obvious adverse effects were investigated during follow-up. CONCLUSIONS: BMMSC transplantation for the treatment of cerebral palsy is safe and feasible, and can improve gross motor and fine motor function significantly. In addition, compared with BMMNC, the motor function of children improved significantly in terms of gross motor and fine motor functions.

Compound Wumei Powder Inhibits the Invasion and Metastasis of Gastric Cancer via Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

To explore the role of CWP in invasion and migration of gastric cancer cells and its underlying molecular mechanism, we performed the experiment in SGC-7901 cells both in vitro and in vivo. In the cell experiment, we evaluated cell proliferation by MTT assay. The results showed that CWP can inhibit the growth of SGC-7901 cells. The influence on cell migration and invasion was detected by wound-healing and Transwell invasion assays. The results showed that the abilities of invasion and migration are restrained in CWP group. Western blot showed that CWP can decrease the expression of Cox-2 and inhibit the PI3K/AKT/GSK3ß/ß-catenin signaling pathway. In the animal experiment, we observed that CWP had an inhibitory effect on the growth of xenograft tumors of nude mice. IHC assay, ELISA, RT-PCR assay, and Western blot assay were used to test relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. The results showed that CWP can suppress relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin pathway. In conclusion, we suggest that CWP inhibits the invasion and metastasis of SGC-7901 cells via Cox-2/PGE2-PI3K/AKT/GSK3ß/ß-catenin signaling pathway.

Clinical and psychometric validation of the quality of life assessment system for advanced gastric cancer based on traditional Chinese medicine.

OBJECTIVE: To establish questionnaire scaling and reliability and examine the clinical and psychometric validity of the quality of life assessment based on Traditional Chinese Medicine for advanced gastric cancer (QLASTCM-Ga). METHODS: The QLASTCM-Ga was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, pretesting and quantitative statistical procedures. The questionnaire was administered to 240 patients diagnosed with advanced gastric cancer before and after treatment. Structured group methods were employed to establish a general and a specifific module respectively. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness. RESULTS: The three identified scales of the QLASTCM-Ga and the total score demonstrated good psychometric properties. Test-retest reliability of the total scale and all domains ranged from 0.90 to 0.94, and internal consistency ranged from 0.86 to 0.93. Correlation and factor analysis demonstrated good construct validity. Signifificant difference in the subscales and the total score were found among groups differing in traditional Chinese medicine syndrome, supporting the clinical sensitivity of the QLASTCM-Ga. Statistically signifificant changes were found for each scale and the total score. Responsiveness was also good. CONCLUSIONS: The QLASTCM-Ga demonstrates good psychometric and clinical validity to assess quality of life in patients with advanced gastric cancer undergoing traditional Chinese medicine therapy. This study is an important fifirst step for future research in this area.