Effects of motor imagery training on gait performance in individuals after stroke: a systematic review and meta-analysis.

PURPOSE: This review systematically explores and summarise the effects of motor imagery training (MIT) compared to conventional therapy on gait performance in individuals after stroke. MATERIALS AND METHODS: Randomised controlled trials (RCTs) were systematically searched in five electronic databases (PubMed, EMBASE, PsycINFO, OVID Nursing and CINAHL) from inception to 30 December 2022. Studies investigating MITs, targeted at individuals after stroke were eligible. Data were extracted related to study and intervention characteristics. RESULTS: Sixteen studies were included. Compared with 'routine methods of treatment or training', the meta-analyses showed that MIT was more effective in improving cadence immediately post intervention (SMD: 1.22, 95% CI: 0.59, 1.85, p = 0.0001, I2 = 25%) and at 1- or 2-months post intervention (SMD: 0.78, 95% CI: 0.35, 1.20, p = 0.0004, I2 = 46%). The results also showed that MIT improves the step length of the affected side and the unaffected side at 1- or 2-months post intervention. Separate meta-analyses were also conducted on different tests of walking endurance (assessed by the 6-Minute Walk Test) and functional mobility (assessed by the Timed-Up-and-Go test). CONCLUSIONS: MIT effectively improved gait performance. The findings in individuals after stroke remain inconclusive due to significant heterogeneity in included studies.

Restoring gait performance and daily functional abilities is an important goal of post-stroke rehabilitation.Motor imagery training (MIT) may be a promising method to improve gait restoration and is expected to provide another option for the effective rehabilitation of stroke patients.This review highlights the limited research on MIT and thus the limited evidence to guide clinical rehabilitation.In the stroke rehabilitation, clinical specialists may consider incorporating MIT into the treatment programme to improve patients' gait performance and ensure effective early lower limb rehabilitation.

Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress.

Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.

Design and evaluation of an intelligent physical examination system in improving the satisfaction of patients with chronic disease.

Background: and Purpose: Enhancing patient satisfaction remains crucial for healthcare quality. The utilization of artificial intelligence (AI) in the Internet of Health Things (loHT) can streamline the medical examination process. Most Traditional Chinese Medicine (TCM) examinations are non-invasive and contribute significantly to patient satisfaction. Our aim was to establish an intelligent physical examination system that amalgamates TCM and Western medicine and to conduct a preliminary investigation into its effectiveness in enhancing the satisfaction of patients with chronic diseases. Materials and methods: Experts from clinical departments, the equipment department, and the software development department were invited to participate in group discussions to determine the design principles and organizational structure of the intelligent physical examination system. This system integrates TCM and Western medicine. We compared the satisfaction levels of patients examined using the intelligent physical examination system with those examined using the traditional medical examination system. Results: An intelligent physical examination system, combining TCM and Western medicine, was developed. A total of 106 patients were finally enrolled (intelligent group vs. control group) to evaluate satisfaction. There were no statistically significant differences between the intelligent group and the control group in age, gender, education, or income level. We identified significant differences in five aspects of satisfaction: 1) the physical examination environment; 2) the attitude and responsiveness of doctors; 3) the attitude and responsiveness of nurses; 4) the effectiveness of obtaining results; and 5) the information regarding physical examination and medical advice (p < 0.05). Furthermore, these differences remained statistically significant even after adjusting for age, gender, education, and income level. Conclusions: The intelligent physical examination system effectively capitalized on the advantages of combining AI with the integration of TCM and Western medicine, substantially optimizing the medical examination process. In comparison to the traditional physical examination system, the intelligent system significantly enhanced patient satisfaction. Future improvements could involve integrating chronic disease follow-up technology into the system.

Metagenomic insights into the rumen epithelial integrity responses to the vitamin B1 supplement under high-concentrate diets treatments.

Subacute ruminal acidosis (SARA) becomes the most common nutritional metabolic disease in high-yielding dairy cows and later fatting beef cattle because of the increasing consumption of high-concentrate diets in modern feeding patterns. Our previous research found a certain piece of evidence that adding 180 mg thiamine/kg DMI could increase the rumen pH and regulate the structure of the rumen microbial community in vivo. However, there is still limited experimental data on the effects of SARA on thiamine status, the damage to the structure of rumen epithelial cells, and the underlying mechanism of the epithelium alterations. For this purpose, a total of 18 Angus bulls (average 22.0-months-old) with an average live weight of 567.6 ± 27.4 kg were randomly allocated into a control treatment (CON), a high-concentrate diet treatment (HC), and a high-concentrate diet with the vitamin B1 supplement treatment (HCB). All bulls were conducted with a 7-day adjustment period followed by a 60-day-long main feeding procedure. Results indicated that ADFI and ADG significantly decreased in the HC treatment compared with CON (P < 0.05), while significantly increased after the VB1 supplement (P < 0.05). Besides, ruminal acetate content was significantly downregulated while propionate was significantly upregulated under the HC treatment compared with CON (P < 0.05); however, these alterations showed a completely inverse regulatory effect on the VB1 supplement compared with HC (P < 0.05). These changes causatively induced a significant decrease in the A/P ratio in the HC treatment compared with CON and HCB treatments (P < 0.05). Bacterial communities in the HC treatment could be separated from those in CON through PCoA axes 1 and 2. Meanwhile, the VB1 supplement significantly altered the bacterial communities compared with the HC treatment, except for HCB-3. Furthermore, the HC treatment significantly upregulated the expression of JNK, Bax, Caspase-8, Caspase-3, Caspase-9, and Cyt-C compared with CON, while significantly downregulated the expression of Bcl-2. The VB1 supplement showed a complete converse gene expression compared with HC. In conclusion, the VB1 supplement could effectively attenuate the alterations that occurred when exposed to high-concentrate diets, and help promote production performance through increased fermentability.

Bioactive components of Banxia Xiexin Decoction for the treatment of gastrointestinal diseases based on flavor-oriented analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD) was first recorded in a Chinese medical classic, Treatise on Febrile Diseases and Miscellaneous Diseases, which was written in the Eastern Han dynasty of China. This ancient prescription consists of seven kinds of Chinese herbal medicine, namely, Pinellia ternata, Rhizoma Coptidis, Radix scutellariae, Rhizoma Zingiberis, Ginseng, Jujube, and Radix Glycyrrhizaepreparata. In clinic practice, its original application in China mainly has focused on the treatment of chronic gastritis for several hundred years. BXD is also effective in treating other gastrointestinal diseases (GIDs) in modern medical application. Despite available literature support and clinical experience, the treatment mechanisms or their relationships with the bioactive compounds in BXD responsible for its pharmacological actions, still need further explorations in more diversified channels. According to the analysis based on the five-flavor theory of TCM, BXD is traditionally viewed as the most representative prescription for pungent-dispersion, bitter-purgation and sweet-tonification. Consequently, based on the flavor-oriented analysis, the compositive herbs in BXD can be divided into three flavor groups, namely, the pungent, bitter, and sweet groups, each of which has specific active ingredients that are possibly relevant to GID treatment. AIM OF THE REVIEW: This paper summarized recent literatures on BXD and its bioactive components used in GID treatment, and provided the pharmacological or chemical basis for the further exploration of the ancient prescription and the relative components. METHOD: ology: Relevant literature was collected from various electronic databases such as Pubmed, Web of Science, and China National Knowledge Infrastructure (CNKI). Citations were based on peer-reviewed articles published in English or Chinese during the last decade. RESULTS: Multiple components were found in the pungent, bitter, and sweet groups in BXD. The corresponding bioactive components include gingerol, shogaol, stigmasterol, and ß-sitosterol in the pungent group; berberine, palmatine, coptisine, baicalein, and baicalin in the bitter group; and ginsenosides, polysaccharides, liquiritin, and glycyrrhetinic acid in the sweet group. These components have been found directly or indirectly responsible for the remarkable effects of BXD on GID. CONCLUSION: This review provided some valuable reference to further clarify BXD treatment for GID and their possible material basis, based on the perspective of the flavor-oriented analysis.

Microfluidic Chip-Based Induced Phase Separation Extraction as a Fast and Efficient Miniaturized Sample Preparation Method.

Induced phase separation extraction (IPSE) is an efficient sample clean-up technique that can replace liquid-liquid extraction (LLE). The purpose of this study was to miniaturize IPSE by carrying it out in a microfluidic chip. An IPSE chip was designed and evaluated for its ability to separate and purify samples on a microscale. The 5 × 2 cm chip was fed with a solution of polar to non-polar model compounds in acetonitrile-water (1:1). In the 100 µm wide and 40 µm deep microchannels, the sample solution was efficiently separated into two immiscible phases by adding a hydrophobic solvent as inducer. Analytes present in the sample solution each migrated to their own favorable phase upon phase separation. After optimization, extraction and fractionation were easily and efficiently achieved. The behavior of analytes with a pH-dependent partitioning could be influenced by adjusting the pH of the sample solution. Scutellaria baicalensis extract, used in Traditional Chinese Medicine (TCM), was successfully separated in aglycones and glycosides. In this microscale system, the sample and solvent consumption is reduced to microliters, while the time needed for the sample pretreatment is less than one minute. Additionally, the extraction efficiency can reach up to 98.8%, and emulsion formation is avoided.

[Start-up and Optimization of Denitrifying Phosphorus Removal in ABR-MBR Coupling Process].

The feasibility of the denitrifying phosphorus removal process in the ABR-MBR system with no sludge reflux and high concentration of seeding activated sludge (25 g ·L-1, in MLSS) in the ABR was investigated. The characteristics of the microbial community in the denitrifying phosphorus removal compartment were also evaluated. The denitrifying phosphorus removal function was achieved by gradually increasing the reflux ratio (R) from 0% to 200%. During the stable operation, the average removal rates of COD, PO43--P, and TN in the system were 88.28%, 54.45%, and 61.93%, respectively. When the influent loading rate, NOx--N reflux ratio, and hydraulic retention time (HRT) of ABR and MBR were 0.8 kg ·(m3 ·d)-1, 150%, and 9 h and 3.3 h, respectively, the average VFA concentration of 80.58 mg ·L-1, ρ(NO2--N)/ρ(NO3--N) reflux ratio of 1.68, and PO43--P and TN removal rates of 64.94% and 62.95% were obtained. The short-cut nitrification denitrifying phosphorus removal was achieved in the ABR-MBR system. Batch tests showed that denitrifying phosphorus removal bacteria (DPAOs) were the main functional bacteria in the ABR, with anaerobic phosphorus release and anoxic phosphorus uptake of 3.73 mg ·L-1 and 10.22 mg ·L-1, respectively. High throughput sequencing results showed that Proteobacteria and Bacteroidetes were the dominant phyla in the phosphorus removal compartment, accounting for 23.49%-53.66% and 16.55%-21.78% of the total phyla, respectively. Thauera, Thiothrix, Pseudomonas, norank_ f_Rhodocyclaceae, and unclassification_ f_Rhodocyclaceae in Proteobacteria, and Sphingobacteriales in Bacteroidetes were the potential denitrifying phosphorus removal microorganisms.

Quality assessment of herbal medicines based on chemical fingerprints combined with chemometrics approach: A review.

Herbal medicine (HM) has been playing a pivotal role in maintaining human health since ancient times, and its therapeutic theory and clinical experience are the precious traditional medical knowledge reserves. As HM occupies an important position in its own right in global healthcare systems, robust quality assessment and control over its complex chemical composition was of great significance to assure its efficacy and safety. Over the past decades, the concept of HM chemical fingerprints aiming to obtain a comprehensive characterization of complex chemical matrices has become one of the most convincing tools for the quality assessment of HM. This review summarizes the recent analytical techniques used to generate HM chemical fingerprints, including chromatography, vibrational spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry. The advantages, drawbacks, and the application scope of each technology have been scrutinized in an attempt to better understand the data analysis. Furthermore, HM fingerprints together with multivariate and multiway chemometrics methods used for different application domains, such as similarity, exploratory, classification, and regression analysis, have also been discussed and illustrated with a few typical studies. The article provides a general picture and workflow of fingerprinting analyses that have been used for the quality assessment of HM.

Profiling and identification of aqueous extract of Cordyceps sinensis by ultra-high performance liquid chromatography tandem quadrupole-orbitrap mass spectrometry.

Characterization of aqueous extract in traditional Chinese medicine (TCM) is challenging due to the poor retention of the analytes on conventional C18 columns. This study presents a systematic characterization method based on a rapid chromatographic separation (8 min) on a polar-modified C18 (Waters Cortecs T3) column of aqueous extract of Cordyceps sinensis. UHPLC-HRMS method was used to profile components in both untargeted and targeted manners by full MS/PIL/dd-MS2 acquisition approach. The components were identified or tentatively identified by reference standards comparison, fragmentation rules elucidation and available databases search. A total of 91 components, including 10 nucleobases, 20 nucleosides, 39 dipeptides, 18 amino acids and derivatives and 4 other components, were characterized from the aqueous extract of C. sinensis. And this was the first time to systematically report the presence of nucleosides and dipeptides in C. sinensis, especially for modified nucleosides. The chemical basis inquiry of this work would be beneficial to mechanism exploration and quality control of C. sinensis and related products. Meanwhile, this work also provided an effective solution for characterization of aqueous extract in TCM.

[Effect of Sludge Retention Time and pH on the Denitrifying Phosphorus Removal Process].

In this work, the effects of the sludge retention time (SRT, 35, 25, or 15 d) and pH (7.5, 8.0, 8.5) on denitrifying phosphorus removal were investigated using denitrifying phosphorus bacteria (DPBs) enriched in a sequencing batch reactor (SBR). The results indicated that shortening the SRT from 35 d to 25 d resulted in a decrease in the mixed liquor volatile suspended solids (MLVSS) from 2821 to 2301 mg·L-1, while the sludge loading rate (F/M) increased from 0.256 kg·(kg·d)-1to 0.312 kg·(kg·d)-1. Although the quantity of net phosphorus release and net phosphorus uptake decreased at this stage, the rates of anaerobic phosphorus release, anoxic phosphorus absorption, and denitrification reached their highest levels with values of 25.07, 15.92, and 9.45 mg·(g·h)-1, respectively, due to the increased sludge activity. Consequently, the phosphorus content of the sludge increased from 4.78% to 5.33%, and the removal rate of PO43--P was stable at above 95% with an average effluent PO43--P concentration below 0.5 mg·L-1. When the SRT was further shortened to 15 d, the MLVSS decreased to values as low as 1448 mg·L-1, and the proportion of DPBs in the phosphorus accumulating organisms (PAOs) decreased from 82.4% to 65.7%, indicating that the DPBs were gradually washed out from the system due to the excessively short SRT. At this stage, the phosphorus content of sludge decreased to 3.43%, while the rates of phosphorus release, phosphorus absorption, and denitrification also decreased to some extent. When the pH was increased (7.5-8.0), the anaerobic phosphorus release rate and the anoxic phosphorus absorption rate also increased, and reached 25.86 mg·(g·h)-1 and 16.62 mg·(g·h)-1, respectively, at a pH of 8.0. When the pH exceeded 8.0, the phosphorus removal efficiency dropped rapidly, supposedly due to phosphorus chemical precipitation.

[Start-up and Stable Operation of ABR-MBR Denitrifying Phosphorus Removal Process].

The nitrogen and phosphorus removal characteristics during the start-up and the long-term operational stability of an anaerobic/anoxic (A/A) ABR coupled aerobic MBR system treating low C/N domestic wastewater were investigated. The results showed that the denitrifying phosphorus bacteria (DPBs) were successfully enriched within 46 d by controlling the nitrate recycling ratio (increasing from 150% to 300%), with a temperature of 30℃±2℃, volume loading rate of 0.8 kg·(m3·d)-1 and sludge reflux ratio of 80% in the ABR, sludge retention time (SRT) in the denitrifying phosphorus removal functional area of 25 d, and the dissolved oxygen (DO) of 1-2 mg·L-1 in the MBR. The net phosphorus release and phosphorus uptake of DPBs reached 20.56 mg·L-1and 27.74 mg·L-1, respectively. Batch tests demonstrated that about 84.8% of phosphorus-accumulating organisms (PAOs) could use NO3--N as an electron acceptor for denitrifying phosphorus removal. After 50 d of stable operation after the successful system start-up, the average removal rates of COD, NH4+-N, TN, and PO43--P were 91.8%, 99.0%, 71.5%, and 94.2%, respectively. The results also suggested that 0.83 mg·L-1NO3--N was consumed per 1 mg·L-1 PO43--P removed during the denitrifying phosphorus removal, indicating that the simultaneous nitrogen and phosphorus removal was achieved in the ABR-MBR system.

Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine.

L-Carnosine (ß-alanyl-L-histidine) is a naturally occurring dipeptide distributed in various organs of mammalians. We previously showed that carnosine inhibited proliferation of human gastric cancer cells through targeting both mitochondrial bioenergetics and glycolysis pathway. But the mechanism underlying carnosine action on mitochondrial bioenergetics of tumor cells remains unclear. In the current study we investigated the effect of carnosine on the growth of human gastric cancer SGC-7901 cells in vitro and in vivo. We firstly showed that hydrolysis of carnosine was not a prerequisite for its anti-gastric cancer effect. Treatment of SGC-7901 cells with carnosine (20 mmol/L) significantly decreased the activities of mitochondrial respiratory chain complexes I-IV and mitochondrial ATP production, and downregulated 13 proteins involved in mitochondrial bioenergetics. Furthermore, carnosine treatment significantly suppressed the phosphorylation of Akt, while inhibition of Akt activation with GSK690693 significantly reduced the localization of prohibitin-1 (PHB-1) in the mitochondria of SGC-7901 and BGC-823 cells. In addition, we showed that silencing of PHB-1 gene with shRNA markedly reduced the mitochondrial PHB-1 in SGC-7901 cells, and significantly decreased the colony formation capacity and growth rate of the cells. In SGC-7901 cell xenograft nude mice, administration of carnosine (250 mg kg/d, ip, for 3 weeks) significantly inhibited the tumor growth and decreased the expression of mitochondrial PHB-1 in tumor tissue. Taken together, these results suggest that carnosine may act on multiple mitochondrial proteins to down-regulate mitochondrial bioenergetics and then to inhibit the growth and proliferation of SGC-7901 and BGC-823 cells.

Characterization and discrimination of steroidal saponins in Tribulus terrestris L. and its three different aerial parts by chemical profiling with chemometrics analysis.

Tribulus terrestris L. is a well-known medicinal plant from subtropical areas. In China Pharmacopoeia, only the fruit of T. terrestris is recorded to be the medicinal part. But some pharmaceutical preparations and food supplements made of total saponins of aerial part of T. terrestris including fruits, stems, and leaves are commercially available. However, steroidal saponins in different parts have not been studied extensively. So differentiating three parts and ensuring reasonable application of T. terrestris has been an important issue. Herein, we developed an integrated platform based on components profiling and chemometrics analysis to comparatively characterize and investigate steroidal saponins in three parts. As a result, a total of 84 steroidal saponins were characterized or tentatively identified, including 20 compounds reported for the first time. A clear separation of the three parts was achieved by partial least squares discriminant analysis based on the identified saponins, and 17 saponins were screened as biomarkers. Support vector machines model established based on 17 markers showed excellent predication accuracy of 100%. Finally, different distribution of steroidal saponins in three parts was shown obviously by heatmap visualization. These results provide promising perspectives for quality control of Chinese medicine, especially those with different medical parts.

Protostemonine attenuates alternatively activated macrophage and DRA-induced asthmatic inflammation.

Asthma is one of the most common pulmonary diseases that threatens human life because of lack of effective medicines. Protostemonine (PSN), an active alkaloid extracted from the roots of Stemona sesslifolia, has anti-inflammatory effects on acute lung injury and acute liver failure. However, it has not been defined whether PSN alleviates asthmatic inflammation. Here, we reported that PSN inhibits pulmonary eosinophil infiltration, goblet cell hyperplasia, mucus secretion, IgE and Th2 cytokine (IL-4, IL-5, IL-13 and IL-33) production by using DRA (dust mites, ragweed and aspergillus)-induced murine asthma model. Moreover, PSN also attenuated the expression of Arginase-1 (Arg-1), Ym-1 and Fizz-1, markers of AAM (alternatively activated macrophage) polarization, in lung tissues. In addition, PSN attenuated IL-4-induced expression of Arg-1, Ym-1 and Fizz-1 in bone marrow derived macrophages (BMDMs). Treatment with PSN decreased IL-4-induced STAT6 phosphorylation, KLF4 and IRF4 expression in BMDMs. Collectively, our results indicated that PSN ameliorates AAM polarization and asthmatic inflammation and might be a potential agent for treating asthma.

[Effect of NOx--N Recycling Ratio on Denitrifying Phosphorus Removal Efficiency in the ABR-MBR Combined Process].

Based on the coupling of the ABR process and the MBR process, a novel combined ABR-MBR process, including biophase separation, liquid circulation, and functional linkage, was developed to achieve simultaneous carbon, nutrient, and phosphorus removal when treating domestic wastewater with low carbon/nitrogen ratio and to obtain the best combination of ABR, providing a quality carbon source, and MBR, achieving shortcut nitrification by optimizing hydraulic retention time (HRT). The influence of NOx--N recycling ratio on nitrogen and phosphorus removal was investigated at NOx--N recycling ratios of 100%, 200%, 300%, and 400%, respectively. The experimental results under different conditions showed that the efficiency of denitrifying phosphorus removal in the ABR was found to increase with increasing NOx--N recycling ratio from 100% to 300% but decreased when the NOx--N recycling ratio was 400%. Shortcut nitrification was achieved by controlling the low dissolved oxygen (DO) concentration ranges from 0.3 to 1.0 mg·L-1 with the short HRT of 3 h in the MBR reactor. The nitrite accumulation ratio was above 60%, when the NOx--N recycling ratio was 300%. Meanwhile, shortcut denitrifying phosphorus removal (where NO2--N mainly acted as the electron acceptor for denitrifying phosphorus removal) was achieved and played the dominant role in phosphorus removal.

[Effect of Volume Loading Rate (VLR) on Denitrifying Phosphorus Removal by the ABR-MBR Process].

The effect of volume loading rate (VLR) on denitrifying phosphorus removal was investigated in a continuous-flow ABR-MBR combined process treating domestic wastewater to arrive at optimum process parameters. In the experiment, the VLR of the ABR was set at 0.76, 1.01, 1.51, and 2.27 kg·(m3·d)-1. The removal of carbon, nitrogen, and phosphorus in the system and the effect of the VLR in the MBR on nitrification performance were observed for each VLR of the ABR. The results showed that under the condition when the VLR of the ABR was 1.51 kg·(m3·d)-1, the amount of COD removal in the A2 chamber was the largest, and shortcut nitrification was achieved in the MBR when the VLR of the MBR was 1.51 kg·(m3·d)-1. Meanwhile, the removal efficiency of NH4+-N and TN reached more than 90% and 72%, respectively, the anaerobic P-release and anoxic P-uptake were 7.41 mg·L-1and 15.42 mg·L-1, respectively, and the concentration of PO43--P in effluent was lower than 0.5 mg·L-1, which indicated that the shortcut nitrification was more conducive to strengthening the performance of denitrifying phosphorus removal in the ABR-MBR system.

Rapid profiling of polymeric phenolic acids in Salvia miltiorrhiza by hybrid data-dependent/targeted multistage mass spectrometry acquisition based on expected compounds prediction and fragment ion searching.

Phenolic acids are the major water-soluble components in Salvia miltiorrhiza (>5%). According to previous studies, many of them contribute to the cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric phenolic acids can be considered as the tanshinol derived metabolites, e.g., dimmers, trimers, and tetramers. A strategy combined with tanshinol-based expected compounds prediction, total ion chromatogram filtering, fragment ion searching, and parent list-based multistage mass spectrometry acquisition by linear trap quadropole-orbitrap Velos mass spectrometry was proposed to rapid profile polymeric phenolic acids in S. miltiorrhiza. More than 480 potential polymeric phenolic acids could be screened out by this strategy. Based on the fragment information obtained by parent list-activated data dependent multistage mass spectrometry acquisition, 190 polymeric phenolic acids were characterized by comparing their mass information with literature data, and 18 of them were firstly detected from S. miltiorrhiza. Seven potential compounds were tentatively characterized as new polymeric phenolic acids from S. miltiorrhiza. This strategy facilitates identification of polymeric phenolic acids in complex matrix with both selectivity and sensitivity, which could be expanded for rapid discovery and identification of compounds from complex matrix.

Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression.

Carnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells HeLa and cervical squamous carcinoma cells SiHa. The results showed that carnosine exerted a significant inhibitory effect on the proliferation of HeLa cells, whereas its inhibitory action on the proliferation of SiHa cells was much weaker. Carnosine decreased the ATP content through inhibiting both mitochondrial respiration and glycolysis pathways in cultured HeLa cells but not SiHa cells. Carnosine reduced the activities of isocitrate dehydrogenase and malate dehydrogenase in TCA (tricarboxylic acid) cycle and the activities of mitochondrial electron transport chain complex I, II, III, and IV in HeLa cells but not SiHa cells. Carnosine also decreased the mRNA and protein expression levels of ClpP, which plays a key role in maintaining the mitochondrial function in HeLa cells. In addition, carnosine induced G1 arrest by inhibiting the G1-S phase transition in both HeLa and SiHa cells. Taken together, these findings suggest that carnosine has a strong inhibitory action on the proliferation of human cervical gland carcinoma cells rather than cervical squamous carcinoma cells. Mitochondrial bioenergetics and glycolysis pathways and cell cycle may be involved in the carnosine action on the cell proliferation in cultured human cervical gland carcinoma cells HeLa.

Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells.

Mass defect filtering-oriented classification and precursor ions list-triggered high-resolution mass spectrometry analysis for the discovery of indole alkaloids from Uncaria sinensis.

Discovery of new natural compounds is becoming increasingly challenging because of the interference from those known and abundant components. The aim of this study is to report a dereplication strategy, by integrating mass defect filtering (MDF)-oriented novelty classification and precursor ions list (PIL)-triggered high-resolution mass spectrometry analysis, and to validate it by discovering new indole alkaloids from the medicinal herb Uncaria sinensis. Rapid chromatographic separation was achieved on a Kinetex® EVO C18 column (<16min). An in-house MDF algorithm, developed based on the informed phytochemistry information and molecular design, could more exactly screen the target alkaloids and divide them into three novelty levels: Known (KN), Unknown-but-Predicted (UP), and Unexpected (UN). A hybrid data acquisition method, namely PIL-triggered collision-induced dissociation-MS2 and high-energy C-trap dissociation-MS3 with dynamic exclusion on a linear ion trap/Orbitrap mass spectrometer, facilitated the acquisition of diverse product ions sufficient for the structural elucidation of both indole alkaloids and the N-oxides. Ultimately, 158 potentially new alkaloids, including 10 UP and 108 UN, were rapidly characterized from the stem, leaf, and flower of U. sinensis. Two new alkaloid compounds thereof were successfully isolated and identified by 1D and 2D NMR analyses. The varied ring E and novel alkaloid-acylquinic acid conjugates were first reported from the whole Uncaria genus. Conclusively, it is a practical chemical dereplication strategy that can enhance the efficiency and has the potential to be a routine approach for the discovery of new natural compounds.