Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 µM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.

The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Characteristics and Effects of Chinese Herbal Medicine in the Management of Female Infertility: A Hospital-Based Study.

BACKGROUND: In Taiwan, Chinese herbal medicine (CHM) is used to treat female infertility. Evidence indicates that the absence of monotherapy efficacy assessment and comparison with mainstream interventions may lead to the improper use of CHM for female infertility. METHODS: A retrospective cohort study enrolled female patients at a hospital undergoing CHM intervention to treat infertility from 2012 to 2020 in order to determine the outcomes of CHM monotherapy for female infertility. Kaplan-Meier analysis under strict assumptions was used to estimate the cumulative probability of pregnancy and live births after CHM. Cox hazard regression analysis was used to estimate the hazard ratios of prognostic variables, namely, the woman's age and diagnostic category. RESULTS: 694 women met the inclusion criteria and accounted for 2,145 cycles. A total of 190 pregnancies resulted in 125 live births, all of which were singleton births of babies with 16 perinatal complications requiring hospitalization. The real cumulative pregnancy rate and cumulative live birth rate (CLBR) for the total population after 10 cycles were between 27.4% and 35.2% and between 18% and 22.1%, respectively. Compared with the live birth rate corresponding to patients aged under 35 years, that of older patients, particularly those aged 38-39 years, was significantly lower (hazard ratio: 0.19, 95% confidence interval: 0.11-0.33). Women with other diagnoses, namely, uterine problems or endometriosis, had a greater probability of a live birth than did women with tubal pathology (hazard ratio: 6.31, 95% confidence interval: 1.99-20.07). CONCLUSION: To the best of our knowledge, this is the first retrospective study to employ life table analysis to determine the CHM treatment outcomes in terms of female infertility. The study established a basis to compare in vitro fertilization (IVF) with CHM and identified the advantages and disadvantages of CHM for treating female infertility. Although the CLBR of present study is lower than those reported in IVF studies, CHM in treating female infertility can still be beneficial to women aged younger than 38 years or with diagnoses other than tubal pathology and worth recommendation by reproductive specialists according to the promising results gained from the strict criteria. However, in order to determine the optimal timing, possible mechanism, corresponding side effects, and the efficacy of CHM combined with IVF for treating female infertility, rigorous research is required.In Taiwan wird die chinesische Heilpflanzenmedizin (CHM) zur Behandlung weiblicher Infertilität angewendet. Es liegen Hinweise vor, nach denen fehlende Wirksamkeitsbeurteilungen der Monotherapien und Vergleiche mit herkömmlichen Interventionen zu einer unsachgemäßen Anwendung von CHM bei weiblicher Infertilität führen können.Eine retrospektive Kohortenstudie schloss Patientinnen eines Krankenhauses ein, die von 2012 bis 2020 wegen Infertilität mit CHM behandelt wurden, um die Behandlungsergebnisse der CHM-Monotherapie bei weiblicher Infertilität zu ermitteln. Zur Schätzung der kumulativen Wahrscheinlichkeit von Schwangerschaften und Lebendgeburten nach einer CHM-Behandlung wurde die Kaplan-Meier-Analyse unter strengen Annahmen verwendet. Mit Hilfe der Cox-Hazard-Regressionsanalyse wurden die Risikoverhältnisse der prognostischen Variablen Alter der Frau und Diagnosekategorie geschätzt.694 Frauen erfüllten die Einschlusskriterien und die Zahl der Zyklen betrug 2,145. Insgesamt 190 Schwangerschaften führten zu 125 Lebendgeburten, allesamt Einlingsgeburten, mit 16 perinatalen Komplikationen, die eine Hospitalisierung erforderten. Die reale kumulative Schwangerschaftsrate und die kumulative Lebendgeburtenrate (cumulative live birth rate, CLBR) für die Gesamtpopulation nach 10 Zyklen lagen zwischen 27.4% und 35.2% bzw. zwischen 18% und 22.1%. Die Lebendgeburtenrate bei älteren Patientinnen, insbesondere im Alter von 38 bis 39 Jahren, war deutlich niedriger als bei Patientinnen unter 35 Jahren (Hazard Ratio: 0.19, 95%-Konfidenzintervall: 0.11­0.33). Bei Frauen mit anderen Diagnosen wie Gebärmutterproblemen oder Endometriose war die Wahrscheinlichkeit einer Lebendgeburt höher als bei Frauen mit Eileitererkrankungen (Hazard Ratio: 6.31, 95%-Konfidenzintervall: 1.99­20.07).Unseres Wissens ist dies die erste retrospektive Studie, in der die Ergebnisse der CHM-Behandlung bei weiblicher Infertilität mittels Sterbetafelanalyse ermittelt wurden. Die Studie bildet eine Grundlage für den Vergleich von In-vitro-Fertilisation (IVF) mit CHM und zeigt die Vor- und Nachteile der CHM zur Behandlung weiblicher Infertilität auf. Zwar fällt die kumulative Lebendgeburtenrate in der vorliegenden Studie niedriger aus als in IVF-Studien, doch kann die CHM bei der Behandlung weiblicher Infertilität für Frauen unter 38 Jahren oder Frauen, die eine andere Diagnose als eine Eileitererkrankung haben, von Nutzen sein und angesichts der vielversprechenden Ergebnisse, die aus den strengen Kriterien gewonnen wurden, ist sie eine Empfehlung durch Reproduktionsspezialisten wert. Allerdings sind rigorose Forschungsarbeiten erforderlich, um die optimale Zeitplanung, den möglichen Mechanismus, die entsprechenden Nebenwirkungen und die Wirksamkeit der CHM in Kombination mit IVF zur Behandlung der weiblichen Infertilität zu ermitteln.

Effects of a prenatal mindfulness program on longitudinal changes in stress, anxiety, depression, and mother-infant bonding of women with a tendency to perinatal mood and anxiety disorder: a randomized controlled trial.

BACKGROUND: Stress is a risk factor for poor physical and mental health, affecting new mothers' ability, especially those with perinatal mood and anxiety disorders, to maintain their everyday lives. Over the past 50 years, global incidences of depression and anxiety disorders have increased, reaching pandemic levels. These incidences represent major public health issues that are challenging to detect and treat. Mindfulness programs are viable for reducing stress, anxiety, and depression. The present study evaluates mindfulness intervention effects on stress, anxiety, depression, and mother-infant bonding. METHODS: We collected data on 102 women participating in a prenatal mindfulness program between July 2021 and March 2022; they were parallel and randomly assigned to experimental or control groups. The intervention group received an 8-week course in a prenatal mindfulness program, and the control group received usual standard prenatal care. The self-reported stress, pregnancy-related anxiety, and depression were assessed before and after the intervention and at 36 weeks of gestation. At 2 and 4 months postpartum, all participants provided self-reported their levels of stress, depression, and quality of mother-infant bonding. RESULTS: Compared to the control group, the experimental group that received the prenatal mindfulness intervention experienced reduced prenatal stress, anxiety, and depression and reduced postnatal stress and depression. Despite this, there was no significant difference between the groups in terms of the quality of mother-infant bonding. CONCLUSIONS: Mindfulness prenatal programs are convenient and effective methods of decreasing stress, anxiety, and depression during the perinatal period. Based on our findings, prenatal mindfulness may play a role in mitigating mood and anxiety disorders and should be considered in future approaches to preventing psychological distress. TRIAL REGISTRATION NUMBER: This trial has been prospectively registered at ClinicalTrials.gov (NCT04693130) and the first registration date was 12/24/2020.

Diosgenin Attenuates Myocardial Cell Apoptosis Triggered by Oxidative Stress through Estrogen Receptor to Activate the PI3K/Akt and ERK Axes.

Cardiovascular diseases in post-menopausal women are on a rise. Oxidative stress is the main contributing factor to the etiology and pathogenesis of cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, is structurally similar to estrogen and has been shown to have antioxidant effects. Therefore, we aimed to investigate the effects of diosgenin in preventing oxidation-induced cardiomyocyte apoptosis and assessed its potential as a substitute substance for estrogen in post-menopausal women. Apoptotic pathways and mitochondrial membrane potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes treated with diosgenin for 1[Formula: see text]h prior to hydrogen peroxide (H2O2) stimulation. H2O2-stimulated H9c2 cardiomyoblast cells displayed cytotoxicity and apoptosis via the activation of both Fas-dependent and mitochondria-dependent pathways. Additionally, it led to the instability of the mitochondrial membrane potential. However, the H2O2-induced H9c2 cell apoptosis was rescued by diosgenin through IGF1 survival pathway activation. This led to the recovery of the mitochondrial membrane potential by suppressing the Fas-dependent and mitochondria-dependent apoptosis. Diosgenin also inhibited H2O2-induced cytotoxicity and apoptosis through the estrogen receptor interaction with PI3K/Akt and extracellular regulated protein kinases 1/2 activation in myocardial cells. In this study, we confirmed that diosgenin attenuated H2O2-induced cytotoxicity and apoptosis through estrogen receptors-activated phosphorylation of PI3K/Akt and ERK signaling pathways in myocardial cells via estrogen receptor interaction. All results suggest that H2O2-induced myocardial damage is reduced by diosgenin due to its interaction with estrogen receptors to decrease the damage. Herein, we conclude that diosgenin might be a potential substitute substance for estrogen in post-menopausal women to prevent heart diseases.

Rapid identification and detection of aristolochic acids in the herbal extracts by Raman spectroscopy.

Herbs containing aristolochic acids (AAs) have already been proven to be highly carcinogenic and nephrotoxic. In this study, a novel surface-enhanced Raman scattering (SERS) identification method was developed. Ag-APS nanoparticles with a particle size of 3.53 ± 0.92 nm were produced by combining silver nitrate and 3-aminopropylsilatrane. The reaction between the carboxylic acid group of aristolochic acid I (AAI) and amine group of Ag-APS NPs was used to form amide bonds, and thus, concentrate AAI, rendering it easy to detect via SERS and amplified to obtain the best SERS enhancement effect. Detection limit was calculated to be approximately 40 nM. Using the SERS method, AAI was successfully detected in the samples of four Chinese herbal medicines containing AAI. Therefore, this method has a high potential to be applied in the future development of AAI analysis and rapid qualitative and quantitative analysis of AAI in dietary supplements and edible herbs.

Taiwan's National Health Insurance at the Emergency Department following the COVID-19 outbreak.

Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.

The Effects of Patchouli Alcohol on Diarrhea-Predominant Irritable Bowel Syndrome are Correlated with Phenotypic Plasticity in Myenteric Neurons and the Targeted Regulation of Myosin Va.

Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.

Electrochemical iron production to enhance anaerobic membrane treatment of wastewater.

Although iron salts such as iron(III) chloride (FeCl3) have widespread application in wastewater treatment, safety concerns limit their use, due to the corrosive nature of concentrated solutions. This study demonstrates that local, electrochemical generation of iron is a viable alternative to the use of iron salts. Three laboratory systems with anaerobic membrane processes were set up to treat real wastewater; two systems used the production of either in-situ or ex-situ electrochemical iron (as Fe2+ and Fe2+(Fe3+)2O4, respectively), while the other system served as a control. These systems were operated for over one year to assess the impact of electrochemically produced iron on system performance. The results showed that dosing of electrochemical iron significantly reduced sulfide concentration in effluent and hydrogen sulfide content in biogas, and mitigated organics-based membrane fouling, all of which are critical issues inherently related to sustainability of anaerobic wastewater treatment. The electrochemical iron strategy can generate multiple benefits for wastewater management including increased removal efficiencies for total and volatile suspended solids, chemical oxygen demand and phosphorus. The rate of methane production also increased with electrochemically produced iron. Economic analysis revealed the viability of electrochemical iron with total cost reduced by one quarter to a third compared with using FeCl3. These benefits indicate that electrochemical iron dosing can greatly enhance the overall operation and performance of anaerobic membrane processes, and this particularly facilitates wastewater management in a decentralized scenario.

A Real-World Study on Ge Gen Tang in Combination with Herbal Medicines for Relieving Common Cold-Associated Symptoms.

Purpose: Real-world evidence refers to patient data derived from the healthcare process. In this study, we used National Health Insurance Research Database (NHIRD) assessments and clinical studies of Ge Gen Tang (GGT, ) in patients with common cold to establish a real-world study model of Traditional Chinese Medicine formulae. GGT is widely prescribed for the treatment of common cold in Taiwan, generally in combination with other medicines. The aim of this study was to determine whether a correlation exists between GGT combined with other medicines and an improvement in cold symptoms. We also established a GGT prescription compatibility system by analyzing Taiwan's NHIRD records for GGT prescription patterns in patients with different types of common cold. Materials and Methods: We extracted and analyzed records from the NHIRD for the period 2000-2015 to determine the most common clinical applications of GGT. GGT and GGT with Chuan Xiung Cha Tiao San were most commonly prescribed for common cold, as per NHIRD recommendations. Records for adults aged 20-65 years who were prescribed GGT for the treatment of common cold (Diagnosis Code ICD-9-460) were included in this study. We assessed the following indicators of the common cold, before and after treatment with GGT: nasal congestion, cough, runny nose, sneezing, sore throat, hoarseness, stiff shoulder, headache, and general physical condition. Results: The cold symptom scores before and after taking the GGT prescriptions significantly differed in the 29 volunteers. The 29 volunteers reported a significantly lower headache severity score after medication than before medication (p < 0.004). Furthermore, patient scores for general physical condition decreased significantly (p < 0.01) after medication.

A self-delivery chimeric peptide for high efficient cell membrane-targeting low-temperature photothermal/photodynamic combinational therapy and metastasis suppression of tumor.

Cellular barriers such as the cell membranes, lysosomes or nuclear pores of tumor cells hinder the drugs delivery and weaken the efficiency of traditional tumor therapies. Targeted destructing tumor cell membranes can quickly destroy cell homeostasis and kill cells without facing intracellular delivery barriers. Herein, we designed a self-delivery phototherapeutic chimeric peptide (CCP) for high efficient cell membrane-targeting combinational low-temperature photothermal therapy (LTPTT) and photodynamic therapy (PDT). The self-assembled CCP nanoparticles display remarkable tumor accumulation after systemic administration without additional carriers, avoiding the carriers related side toxicities. The CCPs are able to generate reactive oxygen species (ROS) and mild heat (<45 °C) locally at cell membrane and quickly induce immunogenic cell death to achieve efficient combinational LTPTT/PDT. The damage-associated molecular patterns released after cell membrane rupture effectively elicit antitumor immunity to eradicate residual tumor cells. With a single dosage and short-term near-infrared (NIR) light irradiation, CCPs significantly inhibit growth and metastasis of tumor, and prolong survival time of tumor-bearing mice. This work presents a unique cell membrane-targeting phototherapy strategy to kill tumor and suppress metastasis in an effective, safe and minimally invasive manner.

Autophagy-inhibiting biomimetic nanodrugs enhance photothermal therapy and boost antitumor immunity.

The instinctive protective stress responses of tumor cells hamper low-temperature photothermal therapy (LTPTT), resulting in tumor recurrence and metastasis. The rapid blood clearance and low-efficiency tumor enrichment of nanomedicines also decrease the efficacy of LTPTT. In this study, we fabricated coassembled photothermal agents (indocyanine green, ICG) and autophagy inhibitors (chloroquine, CQ) and red blood cell and cancer cell hybrid membrane (RCm)-camouflaged ICGCQ@RCm nanoparticles (ICGCQ@RCm NPs) to enhance tumor LTPTT. The ICGCQ@RCm NPs exhibited prolonged blood drug circulation and markedly enhanced drug accumulation in tumor tissues. The ICGCQ@RCm NPs reduced the thermal tolerance of tumor cells to sensitize ICG-mediated LTPTT by inhibiting protective autophagy. The ICGCQ@RCm NPs exerted strong immunogenic cell death (ICD) after efficient LTPTT to activate antitumor immunity. In addition, ICGCQ@RCms optimized the therapeutic efficacy by imaging-guided LTPTT, taking advantage of the near-infrared (NIR) fluorescence of ICG. Consequently, the ICGCQ@RCm NPs effectively inhibited tumors under mild LTPTT, significantly suppressed tumor metastasis and prolonged the survival time of tumor-bearing mice. Furthermore, the ICGCQ@RCm NPs showed high biosafety in vitro and in vivo. The ICGCQ@RCm NPs demonstrated tumor-targeting and imaging-guided autophagy inhibition-sensitized LTPTT using two Food and Drug Administration (FDA)-approved drugs, which have great potential for clinical application.

The prediction values of carbapenemase detection methods and carbapenem susceptibility testing for clinical outcomes of patients with Acinetobacter bacteremia under carbapenem treatment.

BACKGROUND: Carbapenem-resistant Acinetobacter species have emerged as notorious pathogens causing nosocomial infections. Several phenotypic methods have been developed for detecting carbapenemase production in Enterobacteriaceae. The accuracy of these methods in the prediction of carbapenemase production in Acinetobacter species has not been studied well. METHODS: This retrospective study enrolled adult patients with Acinetobacter bacteremia from four medical centers in Taiwan between 2012 and 2016. Their demographics and clinical outcomes were recorded. The carbapenem susceptibility of the Acinetobacter species was determined using the agar diffusion method. The carbapenemase genes were detected by PCR. Four phenotypic methods, including the modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), Carba NP test, and CarbAcineto NP test were carried out to determine the production of carbapenemase. RESULTS: We analyzed 257 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia. Shock within three days of bacteremia and acquisition of carbapenem non-susceptible isolates were independently associated with a higher 14-day and 30-day mortality in patients with Acinetobacter bacteremia. Among the four phenotypic tests for carbapenemase detection, MHT using the imipenem disc displayed the greatest sensitivity (94%; 95% confidence interval [CI], 89-97%) and specificity (81%; 95% CI, 73-88%) for predicting imipenem non-susceptibility. CONCLUSION: Carbapenem non-susceptibility and shock were independent risk factors for mortality in patients with Acinetobacter bacteremia. The MHT could predict the carbapenem susceptibility of Acinetobacter isolates. It is a cheap and quick assay, which could be applied in clinical practice.

New monoterpenoids from the stigmas of Crocus sativus.

One new compound, crocusatin M (1), and three new glycosidic compounds, crocusatins N-P (2-4), along with nine known compounds were isolated from the dried stigmas of Crocus sativus. The structures of new compounds were elucidated on the basis of spectroscopic analysis, and the absolute configurations of 1, 2, and 3 were unambiguously assigned by the comparison of experimental and calculated ECD data. This is the first report of the isolation of 4 with the HMG moiety from the genus Crocus. Compounds 1 and 4 exhibited weak anti-inflammatory activities on inhibiting lipopolysaccharide (LPS)-induced NO production.

Magnolol and Honokiol Inhibited the Function and Expression of BCRP with Mechanism Exploration.

Breast cancer resistance protein (BCRP), one of the ATP-binding cassette (ABC) transporters, was associated with the multidrug resistance (MDR) of chemotherapy. Magnolol (MN) and honokiol (HK) are major bioactive polyphenols of Magnolia officinalis. This study investigated the effects of MN and HK on the function and expression of BCRP for the purpose of developing BCRP inhibitor to overcome MDR. Cell lines including MDCKII-BCRP and MDCKII-WT were used for evaluating the function and expression of BCRP. The results showed that MN (100-12.5 µM) and HK (100-12.5 µM) significantly decreased the function of BCRP by 80~12% and 67~14%, respectively. In addition, MN and HK were verified as substrates of BCRP. Furthermore, MN and HK reduced the protein expression of BCRP, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K). In conclusion, both MN and HK decreased the function and expression of BCRP via EGFR/PI3K signaling pathway. Therefore, both compounds were promising candidates for reversing the MDR of chemotherapy.

Gut microbiota: a potential target for traditional Chinese medicine intervention in coronary heart disease.

Coronary heart disease (CHD) is a common ischaemic heart disease whose pathological mechanism has not been fully elucidated. Single target drugs, such as antiplatelet aggregation, coronary artery dilation and lipid-lowering medicines, can relieve some symptoms clinically but cannot effectively prevent and treat CHD. Accumulating evidence has revealed that alterations in GM composition, diversity, and richness are associated with the risk of CHD. The metabolites of the gut microbiota (GM), including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs), affect human physiology by activating numerous signalling pathways. Due to the advantage of multiple components and multiple targets, traditional Chinese medicine (TCM) can intervene in CHD by regulating the composition of the GM, reducing TMAO, increasing SCFAs and other CHD interventions. We have searched PubMed, Web of science, Google Scholar Science Direct, and China National Knowledge Infrastructure (CNKI), with the use of the keywords "gut microbiota, gut flora, traditional Chinese medicine, herbal medicine, coronary heart disease". This review investigated the relationship between GM and CHD, as well as the intervention of TCM in CHD and GM, and aims to provide valuable insights for the treatments of CHD by TCM.

Recent advance in the discovery of tyrosinase inhibitors from natural sources via separation methods.

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.

[Bayesian network Meta-analysis of traditional Chinese medicine injections combined with antiviral western medicine in treatment of influenza].

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.

Enhancing recovery of bioactive compounds from Cosmos caudatus leaves via ultrasonic extraction.

Cosmos caudatus (C. caudatus) is a medicinal plant that is high in bioactive compounds such as phenolics. In this study, an ultrasound extraction method was used to optimise the extraction of bioactive compounds from C. caudatus leaves. Response surface methodology (RSM) based on a Box-Behnken design (BBD) was applied to obtain the optimum extraction parameters which is solid-liquid ratio (10-30 g/mL), particle size (180-850 µm) and extraction time (20-30 min) for maximal quercitrin and total phenolic content (TPC) yields. Analysis of antimicrobial activity was performed against two human pathogenic microbes: Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by the agar well diffusion method. The optimal ultrasonic extraction condition was as follow: solvent-liquid ratio of 1:28 (g/mL), particle size of 485 µm, and duration of 30 min, respectively. Remarkably, extraction using ultrasonic method had recovered more bioactive content and antioxidant activity than the Soxhlet method. The extract also exhibited good antimicrobial activities. Due to the above findings, the ultrasonic extraction was found to be suitable to improve recovery extraction of quercitrin and TPC from C. caudatus leaves. It also opens the possibility that the plant extract can be used for functional food and antimicrobial agents in various applications.