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The development of dental radiology in Taiwan has been over a century. This study explored mainly the profile of dental radiation workers and their occupational radiation exposure in Taiwan from 2013 to 2020.This study used the secondary data analysis to survey mainly the changes of manpower of the dental radiation workers and their occupational radiation exposure in Taiwan from 2013 to 2020.The number of monitored dental radiation workers increased from 678 in 2013 to 770 in 2020. However, the proportion of monitored dental radiation workers to the total monitored medical radiation workers decreased from 4.29% in 2013 to 3.67% in 2020. Although the number of monitored dental radiation workers increased, the number of the measurably exposed dental radiation workers decreased from 2013 to 2020. The annual collective exposure dose fluctuated from 5.21 man-Sv to 15.47 man-Sv, but it showed a decreasing trend. Furthermore, the mean annual effective exposure dose of total monitored dental radiation workers (0.01-0.02 mSv) and that of the measurably exposed dental radiation workers (0.15-1.11 mSv) were relatively low among various medical radiation workers. In overall, the proportion of medical radiation technologists to dentists varied from 0.41 to 0.45.Although the number of monitored dental radiation workers increase, the number of the measurably exposed dental radiation workers, the proportion of the measurably exposed dental radiation workers to the total monitored dental radiation workers, and the annual collective exposure dose for monitored dental radiation workers decrease from 2013 to 2020.

In Taiwan, dental schools have gradually become a popular choice for high school graduates to enter in the universities. This study mainly analyzed the various admission ways to enroll students into the School of Dentistry of National Taiwan University (SODNTU) from 2000 to 2021.The data on the numbers of enrollees and those enrollees who had completed registration in the SODNTU from 2000 to 2021 were available online to the public and included in this study.The total number of enrollees in the SODNTU over the past 22 years was 764 with an annual mean of 34.73. The registration rate ranged from 90.91% to 100% with a mean registration rate of 96.86% from 2000 to 2021. The examination admission, individual application admission, and numerous stars initiatives admission were the three main admission ways to enroll students into the SODNTU from 2000 to 2021 with a total of 662 enrollees (86.65% of a total of 764 enrollees). The number (proportion) of enrollees through examination admission showed a decreasing trend year by year from 26 (78.79%) in 2000 to 15 (45.45%) in 2021. On the contrary, those enrollees through individual application admission and numerous stars initiatives admission showed an increasing trend year by year from 4 (12.12%) in 2000 to 14 (42.42%) in 2021.Although the examination admission is still the predominant admission way, the individual application admission and numerous stars initiatives admission gradually play pivotal roles to enroll students into the SODNTU recently.

The development of dental assistants in Taiwan has been over a century. This study explored mainly the profile of dental assistants and the occupation survey about them in Taiwan from 2009 to 2021.This study used the documentary analysis and secondary data analysis to survey mainly the changes of manpower of dental assistants in Taiwan from 2009 to 2021, and the association of their wages with economic indicators.According to occupation survey from government, the number of dental assistants increased from 4315 in 2009-7909 in 2021. When estimated based on the data of the United States showing 1.86 dental assistants per dentist, the estimated number of dental assistants increased from 21,113 in 2009 to 28,698 in 2020. Although the mean monthly wage of dental assistants increased from 22,127 NT dollars in 2009 to 26,795 NT dollars in 2021, the proportion of the mean annual wage of dental assistants to the gross domestic product per capita decreased from 47.43% in 2009 to 34.78% in 2021. Moreover, the proportion of the mean monthly wage of dental assistants to the basic monthly wage of labor decreased from 128.05% in 2009 to 111.65% in 2021.In Taiwan, although the manpower and work content of dental assistants are important for dentists, they usually work with a low wage from 2009 to 2021. It is imperative to continue to promote the certification system for dental assistants to improve the professionalism and the wage structure of this occupation.

Taiwanese get use to drinking hand-shaken beverages. However, excessive sugar intake is strongly associated with the occurrence of dental caries. This study evaluated the correlation between the beverage serving activities and the dental use of National Health Insurance (NHI) for common oral diseases in 2016.Data on the population, the beverage serving activities, and the dental records of NHI were obtained from the related websites of government. These data were divided by cities and counties to investigate the beverage serving activities and the dental use of NHI for common oral diseases in 2016.In Taiwan, the value of beverage consumption per person had a moderate to high positive correlation with the dental use rate, the number of out-patient visits per 1,000 people, and the medical expenses per person for common oral diseases. For dental caries, diseases of pulpperiapical tissues, and gingivitisperiodontal diseases, their Pearson's r values were 0.52-0.61, 0.18-0.40, and 0.58-0.65, respectively. These results indicate that the higher the beverage consumption per capita, the higher the dental use per capita.There is a long-term benefit for oral health and systemic health through reducing or avoiding unnecessary excessive sugar intake. Therefore, from a cost-effectiveness viewpoint, Taiwan government should develop a better oral health care policy including a health education strategy of appropriate sugar intake to prevent dental caries and other non-communicable diseases in Taiwanese people.

Breast cancer is the most common cancer in women, and chemotherapy is an effective treatment. However, chemotherapy often causes adverse side effects such as cardiotoxicity, myelosuppression, immunodeficiency, and osteoporosis. Our study focused on the alleviating effects of Anoectochilus roxburghii extracts (AREs) on the adverse side effects of chemotherapy in mice with breast cancer. We individually evaluated the antioxidant capacity and cytotoxicity of the AREs using DPPH and MTT assays. We also examined the effects of the AREs on intracellular F-actin, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) of 4T1 cancer cells before and after doxorubicin (DOX) treatment. Our results showed that ARE treatment enhanced the effects of DOX chemotherapy by promoting cell morphology damage, oxidative stress, and ROS generation, as well as by reducing MMP in the 4T1 breast cancer cells. By using BALB/c mice with breast cancer with DOX treatment, our results showed that the DOX treatment reduced body weight, blood pressure, and heart rate and induced myelosuppression, immunodeficiency, cardiotoxicity, and osteoporosis. After oral ARE treatment of BALB/c mice with breast cancer, the chemotherapeutic effects of DOX were enhanced, and the adverse side effects of DOX chemotherapy were alleviated. Based on the above results, we suggest that AREs can be used as an adjuvant reliever to DOX chemotherapy in BALB/c mice with breast cancer.

With the prevalence of obesity and other components of metabolic syndrome, Non-alcoholic fatty liver disease (NAFLD) has become increasingly common. In recent years, much attention has been paid to various plant sources, hoping to find a treatment for NAFLD in plants. The Livsooth authentic herbal formula (LAH, 樂悠本草), a botanical drug formula combined with Puerariae lobatae radix, Lonicerae japonicae flos, Hoveniae semen, and Siraitiae fructus. This study used a network pharmacology approach to predict the potential mechanisms of LAH against NAFLD. Gene Ontology (GO) and KEGG pathway enrichment analyses have identified potential biochemical and signaling pathways. Subsequently, the potential mechanism of action of LAH on NAFLD predicted by network pharmacology analysis was validated in a high-fat diet (HFD)-induced NAFLD model in C57BL/6 mice. Our results demonstrated that LAH ameliorated hepatocyte steatosis in liver tissue by activating the AMPK pathway and decreasing serum triglycerides, low-density lipoprotein, glucose, and cholesterol. Besides, LAH increased the hepatic antioxidant enzymes activities, suggested that LAH improved oxidative stress markers in HFD induced NAFLD mice. In vitro experiments confirmed that the active component of LAH, puerarin, regulates lipid accumulation through the AMPK pathway. In conclusion, our study shows that network pharmacology predictions are consistent with experimental validation. LAH can be a candidate supplement for the prevention of NAFLD.

Hoi Man Yuen,1 Andy CY Lai,1 Eric KH Liu,2 Ming Chung Lee,2 Winnie CW Chu,2 Joey WY Chan,3 Ngan Yin Chan,3 Yun Kwok Wing,3 Albert M Li,1,4,5 Kate C Chan,1,4,5 Chun Ting Au1,4,5 1Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 2Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 4Laboratory for Pediatric Respiratory Research, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5Hong Kong Hub of Pediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Kate C Chan; Chun Ting Au, Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China, Tel +852 35053515 ; +852 35052917, Fax +852 26360020, Email katechan@cuhk.edu.hk; junau@cuhk.edu.hkBackground: Lateral parapharyngeal wall (LPW) thickness is a potentially useful anatomical marker of childhood obstructive sleep apnea (OSA). Measuring LPW thickness by ultrasonography (USG) is technically feasible but its use in children has not been validated. Therefore, this study aimed to assess the intra- and inter-operator reliability of the sonographic measurements of LPW thickness in children and to assess its validity against magnetic resonance imaging (MRI) measurements.Methods: Prepubertal children aged 6– 11 years suspected to suffer from OSA were recruited. Repeated measurements of LPW thickness by USG were conducted to evaluate the intra- and inter-operator reliability, examined by intraclass correlation coefficient (ICC). LPW thickness was measured as the distance between the internal carotid artery and the echogenic surface of the pharynx in an oblique coronal plane by USG. LPW thickness was measured by MRI at the retropalatal level. The agreement between the LPW thickness measured by USG and MRI was assessed by ICC and Bland-Altman plot.Results: Thirty-four children (mean age: 8.66 ± 1.61, 26 male) were recruited. The intra- and inter-operator reliability of the LPW thickness by USG was good (ICC = 0.84 and 0.82, respectively). The agreement between the USG-measured and MRI-measured LPW thickness was moderate (ICC = 0.72). he Bland-Altman plot demonstrated a mean difference of 0.061 cm and a 95% limit of agreement from 0.91 to 1.12 cm.Conclusion: In this study, we demonstrated that ultrasonography is a valid and reliable method to assess LPW thickness in children. This study was supported by the Direct Grant for Research from the Research Committee of the Chinese University of Hong Kong (Project no. 2020.073).Keywords: pediatric, ultrasound, MRI, obstructive sleep apnea

The augmented velocity index (Avi) is a new Doppler index associated with arterial stiffness. We examined associations of renal Avi with blood pressure (BP), aortic stiffness and carotid intima-media thickness (IMT), and compared its performance with that of resistive index (RI). One hundred forty-seven volunteers were recruited. Renal Avi had significant positive correlations with systolic BP (r = 0.37, p0.001), diastolic BP (r = 0.2, p = 0.016), mean arterial pressure (r = 0.29, p0.001), pulse pressure (r = 0.31, p0.001), carotid-femoral pulse wave velocity (r = 0.49, p0.001) and carotid IMT (r = 0.23, p = 0.005). RI correlated positively with pulse pressure (r = 0.3, p0.001) only. After adjustments for co-variables, the associations remained similar. Patients with abnormal BP values (≥130/80 mm Hg), IMT and aortic stiffness (≥1 standard deviation of mean value) had higher Avi than those with normal values, but not RI. In conclusion, renal Avi had stronger associations with BP, arterial stiffness and carotid IMT than RI in apparently healthy volunteers, and was significantly increased in abnormal patients.

Inflammation plays an important role in the pathophysiology of depression. This study aims to elucidate the antidepressant effect of baicalein, an anti-inflammatory component of a traditional Chinese herbal medicine (Scutellaria baicalensis), on lipopolysaccharide (LPS)-induced depression-like behavior in mice, and to investigate the underlying mechanisms. In vitro, baicalein exhibited antioxidant activity and protected macrophages from LPS-induced damage. The results of the tail suspension test and forced swimming test (tests for despair potential in mice) showed the antidepressant effect of baicalein on LPS-treated mice. It also substantially decreased the production of pro-inflammatory cytokines, including IL-6, TNF-α, MCP-1, and eotaxin, elicited by LPS in the plasma. Baicalein downregulated NF-κB-p65 and iNOS protein levels in the hippocampus, demonstrated its ability to mitigate neuroinflammation. Additionally, baicalein increased the levels of the mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of LPS-treated mice, and elevated the ratio of mBDNF/proBDNF, which regulates neuronal survival and synaptic plasticity. Baicalein also promoted the expression of CREB, which plays a role in a variety of signaling pathways. In summary, the findings of this study demonstrate that the administration of baicalein can attenuate LPS-induced depression-like behavior by suppressing neuroinflammation and inflammation induced by the peripheral immune response.

Non-alcoholic fatty liver disease (NAFLD) has become a prevalent issue and a consequence of metabolic syndrome impact on human health. Both of anti-atherosclerosis and anti-hepatic fibrosis capabilities of herbal medicine Ger-Gen-Chyn-Lian-Tang (GGCLT) has attracted attention, but their molecular regulatory mechanisms in a NAFLD model have not been elucidated. The aim of the present study was to explore the bioactivity ofNAFLD phenotype ofGGCLT not only decreased serum levels of TG and free fatty acids, but glucose and insulin tolerance test inBesides in the liver, modulating of mitochondrial biogenesis and adipose tissue browning were characterized by increased

In traditional Taiwan's society, attending medical school or dental school is usually the greatest aspiration of our students. This study tried to explore the evolution of the tuition and fees for medical education and dental education in Taiwan from 1993 to 2021.This study used the secondary data analysis to survey the changes in the actual amount of the tuition and fees from 1993 to 2021, and the association of tuition and fees with economic indicators.The one-year tuition and fees for medical education increased from 39,020 to 95,200 NT dollars in 1993 to 78,327 and 135,829 NT dollars in 2021 for public and private medical schools, respectively. On the other hand, the one-year tuition and fees for dental education increased from 35,700 to 87,100 NT dollars in 1993 to 71,607 and 130,682 NT dollars in 2021 for public and private dental schools, respectively. Because different increase rates between public and private schools, the gap between tuition and fees per gross domestic product per capita (capita GDP) and those per basic annual salary of labor for public and private schools was shortened year by year.In addition to allowing reasonable increases of tuition and fees, the government should also consider to let the disadvantaged students pay less tuition and fees, assist disadvantaged students through school loans, school grants or scholarships, and improve the opportunities for disadvantaged students to enroll in medical and dental schools through the admission system.

Good oral health is important for general health of the body. This study aimed to evaluate an innovative design incorporating oral health education related to oral pathogenic bacteria into a microbiology laboratory curriculum for students of department of life science by evaluating the students' perspectives on the oral health curriculum.Twenty-six students who took the elective course entitled "Microbiology Laboratory" in the National Taiwan Normal University in 2022 were invited to fill out the questionnaire for a presurvey regarding their familiarity with basic oral health concepts, and a postsurvey in which the students answered the same presurvey questions after finishing the class.Of the 26 students, 25 (96.15%) participated in both the presurvey and postsurvey. The results showed that the learning unit of oral health education related to oral pathogenic bacteria helped students in raising their concepts of oral health. To the questions asking that I understand the bacteria that cause dental caries and the pathogenic mechanism and I understand the bacteria that cause periodontal diseases and the pathogenic mechanism, the numbers of students who agreed both questions increased from 2 (8%) to 25 (100%), respectively. Moreover, the mean scores increased from 2.64 to 4.32 (The learning unit of oral health education in the microbiology laboratory curriculum helped the students of department of life science to increase their awareness and understanding of oral health.

The good oral health plays a pivotal role in improving the general health of the body. The purpose of this study was to evaluate an innovative design incorporating oral health education into a human physiology curriculum for students of early childhood education by evaluating the students' perspectives on the oral health curriculum.Forty-two first-year students who took the compulsory course entitled "Introduction to Human Physiology" in National Taiwan Normal University in 2022 were invited to fill out the questionnaire for a presurvey regarding their familiarity with basic oral health concepts, and a postsurvey in which the students answered the same presurvey questions after finishing the class.Of the 42 students, 41 (97.62%) participated in both the presurvey and postsurvey. The results showed that the learning unit of oral health education helped students in raising their concepts on oral health. To the questions asking that I understand the structure and function of the oral cavity and I understand common oral diseases (dental caries and periodontal diseases), the numbers of students who agreed increased from 12 (29.27%) to 39 (95.12%) and 11 (26.83%) to 36 (87.80%), respectively. Moreover, the mean scores increased from 3.24 to 4.20 (In this study, the learning unit of oral health education in the human physiology curriculum for students of early childhood education helped the students to increase their awareness and understanding of oral health.

There is no specific admission system for dentistry in Taiwan. The aims of this study were to describe and analyze the current admission processes for entry into dental schools through the university admission system and to compare the geographical distribution of dental school enrollees.All seven dental schools of general universities in Taiwan were included to analyze the admission protocols in 2019 and 2020. All data of dental enrollment quotas and dental school enrollees presented in this study were collected from information available to the public on the related websites.The total dental enrollment quotas via the university admission system were 381 in 2019 and 397 in 2020. Those admitted via the special program for indigenous peoples and offshore island peoples were both 27 in 2019 and 2020, respectively. The main dental school admission way was individual application, and the main providers of dental enrollment quotas were northern dental schools and private dental schools. In addition, dental school enrollees were concentrated in the northern region, municipalities, and cities in Taiwan.Further advancement is needed to expand participation and broaden the sociodemographic profile of dental school applicants. The dental schools would benefit from a long-term prospective study about the correlation of admission methods with students' performance in dental schools. The special program is impacting the equality of admission opportunities. It is necessary to track the practice dynamics of these dental school graduates who were enrolled via the special program as a basis for policy adjustment.

Alzheimer's disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to the abnormal accumulation of amyloid β (Aβ) proteins. Yi-Gan-San (YGS), a traditional herbal medicine, has been used for the management of neurodegenerative disorders and for the treatment of neurosis, insomnia and dementia. The aim of this study was to examine antioxidant capacity and cytotoxicity of YGS treatment by using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in vitro. We explored neuroprotective effects of YGS treatment in alleviating Aβ neurotoxicity of Drosophila melanogaster in vivo by comparing survival rate, climbing index, and Aβ expressions through retinal green fluorescent protein (GFP) expression, highly sensitive immunomagnetic reduction (IMR) and Western blotting assays. In the in vitro study, our results showed that scavenging activities of free radical and SH-SY5Y nerve cell viability were increased significantly (

The antioxidant capability of herbal remedies has attracted widespread attention, but their molecular mechanisms in a muscle atrophy model have not been explored. The aim of the present study was to compare the bioactivity of sucrose challenged mice following treatment with ATG-125. Here, through a combination of transcriptomic and biomedical analysis, herbal formula ATG-125, a phytochemical-rich formula, was identified as a protective factor against muscle atrophy in sucrose challenged mice. Gene ontology (GO) identified differentially expressed genes that were primarily enriched in the ‘negative regulation of proteolysis’, ‘cellular amino acid metabolic process’, ‘lipoprotein particle’ and ‘cell cycle’, all of which were associated with the ATG-125-mediated prevention of muscle atrophy, particularly with regard to mitochondrial biogenesis. In skeletal muscle, a set of mitochondrial-related genes, including angiopoietin-like 4, nicotinamide riboside kinase 2 (Nmrk2), pyruvate dehydrogenase lipoamide kinase isozyme 4, Asc-type amino acid transporter 1 and mitochondrial uncoupling protein 3 (Ucp3) were markedly upregulated following ATG-125 intervention. An increase in Nmrk2 and Ucp3 expression were noted after ATG-125 treatment, in parallel with upregulation of the ‘nicotinate and nicotinamide metabolism’ pathway, as determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, KEGG pathway analysis revealed the downregulation of ‘complement and coagulation cascades’, ‘cholesterol metabolism’, ‘biosynthesis of amino acids’ and ‘PPAR signaling pathway’, which were associated with the downregulation of serine (or cysteine) peptidase inhibitor clade A member (Serpina)3, Serpina1b, Serpina1d, Serpina1e, apolipoprotein (Apo)a1 and Apoa2, all of which were cardiovascular and diabetes-associated risk factors and were regulated by ATG-125. In addition, ATG-125 treatment resulted in downregulated mRNA expression levels of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2, troponin-I1, troponin-C1 and troponin-T1 in young adult gastrocnemius muscle compared with the sucrose group. Nuclear factor-κB-hypoxia inducible factor-1α-TGFβ receptor type-II-vascular endothelial growth factor staining indicated that ATG-125 decreased sucrose-induced chronic inflammation. ATG-125 was sufficient to prevent muscle atrophy, and this protective effect may be mediated through upregulation of AKT phosphorylation, upregulating the insulin growth factor-1R-insulin receptor substrate-PI3K-AKT pathway, which in turn resulted in a forkhead box O-dependent decrease in protein degradation pathways, including regulation of atrogin1 and E3 ubiquitin-protein ligase TRIM63. Peroxisome-proliferator activated receptor γ coactivator 1α (PGC1α) was decreased in young adult mice challenged with sucrose. ATG-125 treatment significantly increased PGC1α and significantly increased UCP-1,2,3 expression levels, which suggested ATG-125 poised the mitochondria for uncoupling of respiration. This effect is consistent with the increased SIRT1 levels and may explain an increase in mitochondria biogenesis. Taken together, the present study showed that ATG-125, as an integrator of protein synthesis and degradative pathways, prevented muscle wasting.

A hepatoprotective medicine, Yang-Gan-Wan (YGW), was used to treat hepatic damage in cell and mouse models. We performed a 1,1-diphenyl-2- picrylhydrazyl (DPPH) assay and found that YGW exhibited a significantly high free radical scavenging ability. Furthermore, the results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that YGW treatment could alleviate lipopolysaccharide (LPS)-induced damage in Kupffer cells (liver macrophages). Enzyme-linked immunosorbent assay results demonstrated that YGW treatment could alleviate LPS-induced inflammation in Kupffer cells by inhibiting the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. By quantifying the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), we found that YGW treatment could alleviate hepatic damage and improve immunity in acetaminophen- (APAP-) treated mice by inhibiting the expression of ALT and AST. The findings of hematoxylin and eosin and Masson’s trichrome staining indicated that YGW treatment could alleviate hepatic damage and reduce collagen fiber formation in the liver tissue of APAP-treated mice. Furthermore, immunohistochemistry staining and Western blot results showed that YGW treatment could alleviate oxidative stress, inflammation, and apoptosis in the liver tissue of APAP-treated mice by enhancing superoxide dismutase 2 (SOD2) expression but inhibiting TNF-α and caspase 3 expression. Our results suggest that YGW treatment exerted hepatoprotective effects on LPS-treated Kupffer cells and APAP-treated mice by inhibiting oxidation, inflammation, and apoptosis.

COVID-19 is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The herbal formula, Ping An Fang Yu Yin (PAFYY), has been used to prevent respiratory viral infections for many years. This study aims to evaluate the effect of PAFYY on SARS-CoV-2 infection, oxidative stress, and inflammation via in vitro, investigate the chemical composition by full constituent quantitative analysis, and verify its anti-viral potential against SARS-CoV-2 using in silico. In this study, a total of eleven compounds, twenty amino acids, saccharide compositions, and trace elements were found and quantitatively determined by chromatographic techniques. PAFYY displayed free radical scavenging activity (DPPH, SC50: 1.24 ± 0.09 mg/mL), SOD activity (68.71 ± 1.28%), inhibition of lipoxygenase activity (75.96 ± 7.64 mg/mL) and interfered the interaction of SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (48.04 ± 3.18%). Furthermore, in-silico analysis results supported that liquiritin, 3,5-dicaffeoylquinic acid, and luteolin-7-O-glucoside with the highest affinity between SARS-CoV-2 RBD and human angiotensin-converting enzyme II (hACE2) receptor. Our findings suggest that PAFYY has the potential for anti-SARS-CoV-2 infection, anti-oxidation stress, and anti-inflammation, and may be used as supplements for amelioration or prevention of COVID-19 symptoms, as well as the representative compounds can be used for quality control of PAFYY in the future.

Augmented Velocity Index (Avi) is a new Doppler index developed to quantify velocity changes at the late systolic peak. We examined its reliability, association with arterial stiffness and cardiovascular risk factors. The Avi is calculated as (late systolic peak velocity - early systolic peak velocity)/(highest peak systolic velocity - end-diastolic velocity). Fifty volunteers (mean age ± standard deviation: 43.5 ± 14.2 y, men: 52%) without known medical illnesses or drug use were recruited. Carotid Doppler waveforms with measurements of Avi were recorded. Carotid pressure waveforms were obtained by applanation tonometry for measurement of the Augmentation Index (AI). Clinical measurements including body mass index (BMI) and blood pressure (BP) were assessed, and fasting blood was taken for measurement of glycemia and lipid profile. Another 15 volunteers (age range: 22-60 y, men: 33.3%) were recruited to study the reliability of Avi measurement. The results revealed that carotid Avi closely correlated with the index of arterial stiffness, AI (r = 0.76, p0.001) on Pearson correlation. On multiple linear regression analysis, Avi remained a significant independent determinant of AI after adjustments for clinical variables. The Avi had significant associations with cardiovascular risk factors (age, BMI, total cholesterol, low-density lipoprotein cholesterol, systolic and diastolic BP). The intra-class correlation coefficients for inter-observer and intra-observer reliability of Avi measurements were 0.93 (95% confidence interval [CI]: 0.8-0.98) and 0.97 (95% CI: 0.92-0.99) respectively. In conclusion, the Avi is a reproducible new Doppler index, independently associated with arterial stiffness in terms of the AI, which initially correlated with cardiovascular risk factors.

Doxorubicin (DOX), a chemotherapeutic drug, often causes many adverse side effects in patients with cancer, such as weight loss, motor disability, blood circulation defects, myelosuppression, myocardial injury, joint degeneration, and bone loss. The Chinese herbal medicine Guilu Erxian Glue (GEG) has been used in the prevention and treatment of osteoarthritis and osteoporosis for hundreds of years, with considerably fewer side effects. We expected that GEG could serve as a protective and beneficial alternative treatment for DOX-induced adverse side effects. In this study, we evaluated whether GEG can alleviate DOX-induced weight loss, motor disability, abnormal blood circulation, myelosuppression, myocardial injury, joint degeneration, and bone loss by using chemotherapy models of synoviocyte cell line HIG-82 and mice. Moreover, we examined the antioxidant capacity of GEG by using DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical scavenging. Our results revealed that GEG treatment can significantly enhance DPPH free-radical scavenging and reduce DOX-induced cytotoxicity in synoviocyte HIG-82 cells. In addition, GEG treatment for 2 weeks can significantly relieve weight loss, enhance exhaustive exercise capacity, improve blood circulation, alleviate myocardial oxidative stress and inflammation, and strengthen the tibias of DOX-treated mice. Thus, we suggest that GEG treatment can be a protective and alternative therapy for alleviating chemotherapy-related side effects such as weight loss, motor disability, blood circulation defects, and bone loss.

Rhizoma Coptidis is a popular phytomedicine for the treatment of type 2 diabetes in Asia, but its effective dose for diabetes treatment remains confused because of diverse origins. This study aimed to investigate the dose-response effects of Rhizoma Coptidis extract granules (RCEG), produced with standardized quality control, on hypoglycemic effects in patients with type 2 diabetes. We conducted a retrospective analysis of Chang Gung Research Database from January 01, 2008 to November 30, 2017. Outpatients visiting traditional Chinese medicine clinics and receiving RCEG for type 2 diabetes treatment were included. Plasma glucose, lipid, and other parameters were analyzed from 93 patients with a total of 737 visits within 60 weeks. Scatter plots with the LOESS analysis were used to explore the association between RCEG dose and hypoglycemic effect. The minimal effective dose was chosen to divide the study population into the high-dose and low-dose RCEG groups. Non-parametric tests were used for between-group and within-group comparisons. The multivariate nonlinear mixed-effects model was applied to access the effect of treatment length and groups simultaneously on the change of HbA1c and fasting plasma glucose. The “arule” package in R was used to present the network diagram of RCEG and other co-prescriptions. We first discovered a significant relationship between RCEG dose and HbA1c reduction when the dose reached 0.08 g/kg/day or higher. We thus defined 0.08 g/kg/day of RCEG as the minimum effective dose, and a threshold to separate patients into the high-dose (≥0.08 g/kg/d) and low-dose (

Weanling piglets often develop respiratory diseases such as pneumonia because they encounter substantial environmental stress. This study investigated an alternative herbal feed additive, Guizhi Li-Zhong Tang (GLZ), for preventing pneumonia in weanling piglets. An in vitro experiment demonstrated that GLZ has high antioxidant capacity and low cytotoxicity toward Kupffer cells. In addition, GLZ treatment can alleviate lipopolysaccharide (LPS)-induced damage in Kupffer cells. A total of 94 4-week-old piglets were randomly divided into three groups, which received sham treatment, 0.2% Tilmicosin antibiotic (TAB) treatment, or 0.2% GLZ treatment. Piglets receiving the GLZ treatment had a higher survival rate and higher immunoglobulin G levels but lower allergy-related eosinophil levels and cough incidence than did piglets receiving the sham or 0.2% TAB treatments. Through immunohistochemistry and Western blot analysis, we discovered that piglets receiving the 0.2% GLZ treatment had significantly higher expression of antioxidant-related SOD2 and lower expression of oxidative-stress-related 3-NT ( p < 0.01 ), inflammation-related TNF-α ( p < 0.01 ) and NF-κB ( p < 0.05 ), and apoptosis-related caspase-3 ( p < 0.01 ) in lung tissue than did piglets receiving the sham or 0.2% TAB treatment. Therefore, GLZ treatment is promising as an alternative to antibiotic medicine for weanling piglets because of its protective antioxidative, anti-inflammatory, and antiapoptotic effects in lung tissue.

Amyloid β (Aβ) plays a major role in the neurodegeneration of Alzheimer's disease (AD). The accumulation of misfolded Aβ causes oxidative stress and inflammatory damage leading to apoptotic cell death. Traditional Chinese herbal medicine (CHM) has been widely used in treating neurodegenerative diseases by reducing oxidative stress and neuroinflammation. We examined the neuroprotective effect of formulated CHM Shaoyao Gancao Tang (SG-Tang, made of Paeonia lactiflora and Glycyrrhiza uralensis at 1:1 ratio) in AD cell and mouse models. In Aβ-GFP SH-SY5Y cells, SG-Tang reduced Aβ aggregation and reactive oxygen species (ROS) production, as well as improved neurite outgrowth. When the Aβ-GFP-expressing cells were stimulated with conditioned medium from interferon (IFN)-γ-activated HMC3 microglia, SG-Tang suppressed expressions of inducible nitric oxide synthase (iNOS), NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, attenuated caspase-1 activity and ROS production, and promoted neurite outgrowth. In streptozocin-induced hyperglycemic APP/PS1/Tau triple transgenic (3×Tg-AD) mice, SG-Tang also reduced expressions of NLRP1, NLRP3, Aβ and Tau in hippocampus and cortex, as well as improved working and spatial memories in Y maze and Morris water maze. Collectively, our results demonstrate the potential of SG-Tang in treating AD by moderating neuroinflammation.

The study mainly investigated the effects of Chinese veterinary medicine B307 in cardiac and motor functions in animal models of pigeons and mice. Related cellular mechanisms were also studied in the neuroblastoma cell model of SH-SY5Y. Cardiac functions of pigeons and mice were examined by using moorFLPI Laser color Doppler imager and M-mode echocardiography, and motor functions were examined by using muscle electrical stimulation and force recording in the isolated breast muscle. Intracellular calcium levels and electrical activity of SH-SY5Y cells were examined by using Fura 2-AM fluorescence and MED64 system separately. Our results in vivo found that those pigeons under oral B307 treatment obviously enhanced subcutaneous microcirculation and contractile force and prolonged fatigue time in their breast muscles. Those mice under oral B307 treatment obviously elevated ejection fraction and cardiac output in their hearts. Our results in vitro showed that those SH-SY5Y cells under B307 treatment obviously increased intracellular calcium mobilization and electrical activities. These results revealed that improvement of cardiac and motor functions under B307 treatments may be caused by increasing electrical activities and intracellular calcium levels in neuromuscular cells and a similar mechanism may also occur in muscle cells. Thus, we suggested that B307 can be a functional Chinese veterinary medicine for flying pigeons.

Alzheimer’s disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to the abnormal accumulation of amyloid β (Aβ) proteins. Yi-Gan-San (YGS), a traditional herbal medicine, has been used for the management of neurodegenerative disorders and for the treatment of neurosis, insomnia and dementia. The aim of this study was to examine antioxidant capacity and cytotoxicity of YGS treatment by using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in vitro. We explored neuroprotective effects of YGS treatment in alleviating Aβ neurotoxicity of Drosophila melanogaster in vivo by comparing survival rate, climbing index, and Aβ expressions through retinal green fluorescent protein (GFP) expression, highly sensitive immunomagnetic reduction (IMR) and Western blotting assays. In the in vitro study, our results showed that scavenging activities of free radical and SH-SY5Y nerve cell viability were increased significantly (p < 0.01–0.05). In the in vivo study, Aβ42-expressing flies (Aβ42-GFP flies) and their WT flies (mCD8-GFP flies) were used as an animal model to examine the neurotherapeutic effects of YGS treatment. Our results showed that, in comparison with those Aβ42 flies under sham treatments, Aβ42 flies under YGS treatments showed a greater survival rate, better climbing speed, and lower Aβ42 aggregation in Drosophila brain tissue (p < 0.01). Our findings suggest that YGS should have a beneficial alternative therapy for AD and dementia via alleviating Aβ neurotoxicity in the brain tissue.

BACKGROUND AND PURPOSE Bumetanide has anxiolytic effects in rat models of conditioned fear. As a loop diuretic, bumetanide blocks cation-chloride co-transport and this property may allow bumetanide to act as an anxiolytic by modulating GABAergic synaptic transmission in the CNS. Its potential for the treatment of anxiety disorders deserves further investigation. In this study, we evaluated the possible involvement of the basolateral nucleus of the amygdala in the anxiolytic effect of bumetanide. EXPERIMENTAL APPROACH Brain slices were prepared from Wistar rats. extracellular recording, stereotaxic surgery, fear-potentiated startle response, locomotor activity monitoring and Western blotting were applied in this study. KEY RESULTS Systemic administration of bumetanide (15.2 mg·kg-1 , i.v.), 30 min prior to fear conditioning, significantly inhibited the acquisition of the fear-potentiated startle response. Phosphorylation of ERK in the basolateral nucleus of amygdala was reduced after bumetanide administration. In addition, suprafusion of bumetanide (5 or 10 μM) attenuated long-term potentiation in the amygdala in a dose-dependent manner. Intra-amygdala infusion of bumetanide, 15 min prior to fear conditioning, also blocked the acquisition of the fear-potentiated startle response. Finally, the possible off-target effect of bumetanide on conditioned fear was excluded by side-by-side control experiments. CONCLUSIONS AND IMPLICATIONS These results suggest the basolateral nucleus of amygdala plays a critical role in the anxiolytic effects of bumetanide.

Antrodia cinnamomea (AC) exhibits many bioactivities, including anti-inflammatory, anti-cancer, and hepatoprotection activities. Many researchers have studied the functions of the components or fractions of AC, but the functions of the original extractions of AC have not been studied. In addition, the detailed relationship between AC and immune-related signaling pathways is unclear. In this study, we screened the effects of CCM111, which is the extract of AC, on seven immune-related signaling pathways and further investigated whether CCM111 can influence inflammation. Interestingly, our results showed that CCM111 significantly inhibited the IL-6-stimulated STAT3 pathway and the LPS-stimulated NF-κB pathway in macrophages. CCM111 also decreased the phosphorylation of STAT3, Tyk2 and the nuclear translocation of p65. Moreover, CCM111 and F4, a fraction of CCM111, down-regulated nitric oxide (NO) production, the protein levels of iNOS and COX-2, and inflammatory cytokines in macrophage cells. Therefore, our study suggested that CCM111 has the potential to be developed as an effective anti-inflammatory agent.

In Taiwan, the herbal formula B401 is considered as a health supplement for middle-aged women that can alleviate sweating, anxiety, and sleep disorders. However, the relevant mechanisms are still unclear. In this study, we evaluated the beneficial effects of the herbal formula B401 therapy in the reproductive regulation of ovariectomised mice. Female ICR mice were randomised into four groups: wild-type (WT) mice with sham treatment, wild-type mice treated with the herbal formula B401, bilateral ovariectomised (OVX) mice with sham treatment, and bilateral ovariectomised mice treated with the herbal formula B401. Mice were orally given the herbal formula B401 at a dose of 30 mg/kg bw/day for 2 weeks. At the end of oral treatment with sham or the herbal formula B401, levels of reactive oxygen species (ROS), calcium, phosphorus, and estradiol-17βin the blood; uterine weight and endometrial thickness; and expressions of estrogen receptorα(ERα), estrogen receptorβ(ERβ), progesterone receptor (PR), vascular endothelial growth factor (VEGF), and superoxide dismutase 2 (SOD2) in the uterine tissue were examined and then compared among the four groups of mice. We found that OVX mice decreased levels of calcium, phosphorus, and estradiol-17βin the blood, decreased uterine weight and endometrial thickness, and decreased expressions of ERα, ERβ, PR, and SOD2 in the uterine tissue but increased blood ROS levels compared with those of WT mice. In addition, OVX mice with the herbal formula B401 therapy can increase levels of calcium, phosphorus, and estradiol-17βin the blood, increase uterine weight and endometrial thickness, and increase expressions of ERα, ERβ, PR, VEGF, and SOD2 in the uterine tissue but decrease blood ROS levels. Our results may provide reasonable explanation for the reproductive regulation of the herbal formula B401 therapy.

Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular β-amyloid (Aβ) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Aβ deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Aβ aggregate reducers could be effective for AD treatment. Using a Trx-His-Aβ biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Aβ aggregation. Treating Tet-On Aβ-GFP 293 cells with these compounds reduced Aβ aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Aβ-GFP SH-SY5Y cells. Furthermore, treatment with above compounds improved neuronal cell viability, neurite outgrowth, and synaptophysin expression level in mouse hippocampal primary culture under oligomeric Aβ-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Aβ-induced inhibition of hippocampal long-term potentiation in mouse hippocampal slices. Our results demonstrate how synthetic indolylquinoline compounds are likely to work as chemical chaperones in Aβ-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment.

Misfolded tau proteins induce accumulation of free radicals and promote neuroinflammation by activating microglia-releasing proinflammatory cytokines, leading to neuronal cell death. Traditional Chinese herbal medicines (CHMs) have been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of formulated CHMs Bai-Shao (made of Paeonia lactiflora), Gan-Cao (made of Glycyrrhiza uralensis), and Shaoyao Gancao Tang (SG-Tang, made of P. lactiflora and G. uralensis at 1 : 1 ratio) in cell model of tauopathy. Our results showed that SG-Tang displayed a greater antioxidative and antiaggregation effect than Bai-Shao and Gan-Cao and a stronger anti-inflammatory activity than Bai-Shao but similar to Gan-Cao. In inducible 293/SH-SY5Y cells expressing proaggregant human tau repeat domain (ΔK280 tauRD), SG-Tang reduced tau misfolding and reactive oxygen species (ROS) level in ΔK280 tauRD 293 cells and promoted neurite outgrowth in ΔK280 tauRD SH-SY5Y cells. Furthermore, SG-Tang displayed anti-inflammatory effects by reducing nitric oxide (NO) production in mouse BV-2 microglia and increased cell viability of ΔK280 tauRD-expressing SH-SY5Y cells inflamed by BV-2 conditioned medium. To uncover the neuroprotective mechanisms of SG-Tang, apoptosis protein array analysis of inflamed tau expressing SH-SY5Y cells was conducted and the suppression of proapoptotic proteins was confirmed. In conclusion, SG-Tang displays neuroprotection by exerting antioxidative and anti-inflammatory activities to suppress neuronal apoptosis in human tau cell models. The study results lay the base for future applications of SG-Tang on tau animal models to validate its effect of reducing tau misfolding and potential disease modification.

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-β/Smad signaling in a dose-dependent manner compared with CCl4 treatment alone. CCM111 markedly inhibited TGF-β, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl4-induced liver fibrosis by the cooperative inhibition of TGF-β-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases. Keywords: Antrodia cinnamomea, Liver fibrosis, STAT3 pathway, TGF-β pathway, Wnt pathway

Objective Currently, the cosmetic and medical industries are paying considerable attention to solve or prevent skin damage or diseases, such as hyperpigmentation and oxidation and free radical damage. In this study, the effective compounds in Myrica rubra fruit were extracted and studied the biological effects of these M. rubra fruit extracts. Methods In this study, we extracted M. rubra fruit using solutions with various ratios of water to ethanol (100:0, 50:50, 5:95) and studied the anti-melanogenesis, anti-oxidation and radical scavenging effects of these M. rubra fruit extracts on two melanoma cell lines: mouse melanoma (B16-F0) and human melanoma (A2058). The cytotoxicity, melanin synthesis, mushroom and cellular tyrosinase activities, enzyme kinetics, melanogenesis-related gene expression, melanogenesis-related protein secretion, radical DPPH scavenging activity and ROS inhibition after treatment with M. rubra fruit extracts were determined. Results The results showed that the water extract of M. rubra fruit was less cytotoxic to the melanoma cell lines, effectively inhibited melanin synthesis and tyrosinase activity and down-regulated the gene expression and protein secretion of MITF and TRP-1. In addition, the M. rubra fruit extracts also showed the abilities to scavenge DPPH free radicals and suppress ROS production. Finally, the effective compounds in the water extract were Myricetin-O-deoxyhexoside, Quercetin-O-deoxyhexoside, and Kaempferol-O-hexoside determined by LC/MS/MS assay. Conclusion Overall, the water extract of M. rubra fruit is a safe and effective melanin inhibitor and anti-oxidant and can be applied widely in the fields of cosmetics and medicine.

BackgroundIn Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes.MethodsForty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation.ResultsAt week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial.ConclusionsThis pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

As a practical and safe herbal medicine, the seeds of Brucea javanica (L.) Merr., were used to cure patients suffering from infectious diseases such as malaria. Recent advances revealed that the herb could also be a useful cancer therapy agent. The study demonstrated that aqueous B. javanica (BJ) extract attenuated the growth of human non-small-lung cancer cells bearing mutant L858R/T790M epidermal growth factor receptor (EGFR). The reduced cell viability in H1975 cells was attributed to apoptosis. Transfection of EGFR small hairpin RNA reverted the sensitivities. When nude mice were fed BJ extract, the growth of xenograft tumors, as established by H1975 cells, was suppressed. Additional histological examination and fluorescence analysis of the resected tissues proved that the induced apoptosis mitigated tumor growth. The work proved that the BJ extract exerted its effectiveness by targeting lung cancer cells carrying mutated EGFR while alleviating tumorigenesis. Aqueous BJ extract is a good candidate to overcome drug resistance in patients undergoing target therapy.

Seung-Hun Kim,1,* Chun-Yen Liu,1,* Po-Wei Fan,1 Chang-Heng Hsieh,1 Hsuan-Yuan Lin,1 Ming-Chung Lee,2 Kang Fang1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Brion Research Institute of Taiwan, New Taipei City, Taiwan *These authors contributed equally to this work Abstract: As a practical and safe herbal medicine, the seeds of Brucea javanica (L.) Merr., were used to cure patients suffering from infectious diseases such as malaria. Recent advances revealed that the herb could also be a useful cancer therapy agent. The study demonstrated that aqueous B. javanica (BJ) extract attenuated the growth of human non-small-lung cancer cells bearing mutant L858R/T790M epidermal growth factor receptor (EGFR). The reduced cell viability in H1975 cells was attributed to apoptosis. Transfection of EGFR small hairpin RNA reverted the sensitivities. When nude mice were fed BJ extract, the growth of xenograft tumors, as established by H1975 cells, was suppressed. Additional histological examination and fluorescence analysis of the resected tissues proved that the induced apoptosis mitigated tumor growth. The work proved that the BJ extract exerted its effectiveness by targeting lung cancer cells carrying mutated EGFR while alleviating tumorigenesis. Aqueous BJ extract is a good candidate to overcome drug resistance in patients undergoing target therapy. Keywords: Brucea javanica, target therapy, epidermal growth factor receptor, human lung, herbal medicine, apoptosis

Rhubarb (Rheum tanguticum; da-huang in Chinese medicine) is a herbal medicine that has been used widely for managing fever and removing toxicity. In this study, we investigated how rhubarb inhibits influenza virus during the early stage of the infectious cycle using different functional assays. A non-toxic ethanolic extract of rhubarb (Rex) inhibited several H1N1 subtypes of influenza A viruses in Madin–Darby canine kidney cells, including strains that are clinically resistant to oseltamivir. Time course analysis of Rex addition showed that viral entry was one of the steps that was inhibited by Rex. We also confirmed that Rex effectively inhibited viral attachment and penetration into the host cells. The inhibition of red blood cell haemolysis and cell–cell fusion by Rex suggests that Rex may block haemagglutinin-mediated fusion (virus–endosome fusion) during the fusion/uncoating step. Rex has the capacity to inhibit influenza viruses by blocking viral endocytosis. Thus, rhubarb might provide an alternative therapeutic approach when resistant viruses become more prevalent.

Resveratrol is a natural polyphenol and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and myocardial infraction. Parkinson's disease is a common progressive neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the most useful neurotoxin to induce Parkinsonism. The present study was carried out to elucidate the neuroprotective effect and possible mechanism of resveratrol on MPTP-induced striatal neuron loss. Sixty adult Balb/c mice were divided into four groups: sham operation, MPTP treatment (30 mg/kg, i.p.), MPTP combined with resveratrol administration (20 mg/kg, i.v.), and resveratrol treatment alone. Microdialysis and high-performance liquid chromatography were used to analyze dihydroxybenzoic acid (DHBA) that reflected the hydroxyl radical level. In the present study, we found MPTP chronic administration significantly induced motor coordination impairment in mice. After MPTP administration, the hydroxyl radical levels in substantia nigra were also significantly elevated and animals displayed severe neuronal loss. Resveratrol administration significantly protected mice from MPTP-induced motor coordination impairment, hydroxyl radical overloading, and neuronal loss. Our results demonstrated that resveratrol could elicit neuroprotective effects on MPTP-induced Parkinsonism through free radical scavenging.

The leaves of Perilla frutescens (L.) Britt. have been traditionally used as an herbal medicine in East Asian countries to treat a variety diseases. In this present study, we investigated the inhibitory effects of P. frutescens extract (PFE) on N-formyl-Met-Leu-Phe (fMLF)-stimulated human neutrophils and the underlying mechanisms. PFE (1, 3 and 10 μg/ml) inhibited superoxide anion production, elastase release, reactive oxygen species formation, CD11b expression and cell migration in fMLF-activated human neutrophils in dose-dependent manners. PFE inhibited fMLF-induced phosphorylation of the Src family kinases (SFKs), Src (Tyr416) and Lyn (Tyr396) and reduced their enzymatic activities. Both PFE and PP2 (a selective inhibitor of SFKs) reduced the phosphorylation of Burton’s tyrosine kinases (Tyr223) and Vav (Tyr174) in fMLF-activated human neutrophils. Additionally, PFE decreased intracellular Ca2+ levels ([Ca2+]i), whereas PP2 prolonged the time required for [Ca2+]i to return to its basal level. Our findings indicated that PFE effectively regulated the inflammatory activities of fMLF-activated human neutrophils. The anti-inflammatory effects of PFE on activated human neutrophils were mediated through two independent signaling pathways involving SFKs (Src and Lyn) and mobilization of intracellular Ca2+.

A computer-based video analysis system has been developed for measuring the stroke volume and the heart rate of the insect. A quantitative evaluation of the effects of octopamine (OA) on the heart rate, stroke volume and cardiac output of Periplaneta americana, the American cockroach, was also studied. The heart rate of OA-treated cockroach significantly increased within 2 minutes, compared to that of the control groups. On the other hand, the stroke volumes of OA-treated cockroaches decreased within 2 minutes (p < 0.05). Furthermore, OA elicited the heart rate and the stroke volume with a dose- dependent response. Although OA increased heart rate and decreased stroke volume in the cockroach, it decreased cardiac output (mL/min) calculated based on heart rate (beats/min) and stroke volume (mL/beat).

Two high-performance liquid chromatographic methods, one combined with a photodiode array detector (LC/UV) and another with mass spectrometry (LC/MS), were developed for the analysis of aristolochic acid I and II in herbal medicines. The LC/UV method was carried out using a Cosmosil 5C18-MS column with a gradient solvent system composed of phosphate buffer-acetonitrile and a UV detector (390 nm). The LC/MS method was performed using an acetate buffer-acetonitrile solvent system and positive-ion electrospray ionization MS. The characteristic fragment ions for aristolochic acid I were selected at m/z 359, m/z 324, m/z 298, and m/z 296, and for aristolochic acid II at m/z 329, m/z 294, and m/z 268. In order to attain better resolution, solid phase extraction was used to prepare the test solution in this study.

Silicone fluid is applied to reduce the friction of medical device in this study. Several factors, which might affect the friction of Arterial-Venous Fistula (A. V.F.) Needles, were investigated by a series of experiments. The experimental results showed that a better condition for the coating is using 10/90-weight ratio of MDX4/n-hexane silicone solution and dipping for 1.5 seconds. Two-step coating with an interval of 20 minutes also was examined to give an improvement in the lubricity of needles. It was observed that increased DC 360 concentration in coating solution displays more excellent friction reduction properties. Experimental consequences also showed that the lubricity of needles coated with DC 360 (350cst) is superior to that of coated with DC 360 (12,500cst).

Background Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic antimyeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1.3 mg/m(2) on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators’ assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6.47 months (IQR 1.81-13.47) in the panobinostat group and 5.59 months (2.14-11.30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11.99 months [95% CI 10.33-12.94] vs 8.08 months [7.56-9.23]; hazard ratio [HR] 0.63, 95% CI 0.52-0.76; p

A method combining the techniques of micellar electrokinetic capillary chromatography (MECC) and capillary zone electrophoresis (CZE) has been developed to assay seventeen alkaloids in coptis-evodia herb couple. The MECC method, based on SDS, was applied to analyze three indolequinazoline alkaloids and six quinolone alkaloids in evodia within 30 minutes, and a CZE technique was used to determine eight quaternary alkaloids (dehydroevodiamine in evodia, and seven protoberberine alkaloids in coptis) within 25 minutes. The recovery efficiencies were 96.68–103.19% in MECC and 99.65–103.28% in CZE, with a relative standard deviation of 1.67–4.00% for MECC and 2.33–4.38% for CZE. The calibration curves exhibited good linearity over one order of magnitude of concentration, and their minimum detectable concentrations were approximately 15.78 to 47.33 μ/mL using a 0.75 μ inner diameter column. Contents of the seventeen alkaloids in a methanol-water crude extract of coptis-evodia herb couple could easily be...

A total of ten Evodia alkaloids was separated successfully by micellar electrokinetic capillary chromatography (MECC) and capillary zone electrophoresis (CZE). The MECC method based on SDS was applied to analyze three indolequinazoline alkaloids (evodiamine, rutaecarpine and carboxyevodiamine) and six quinolone alkaloids (1-methyl-2-nonyl-4(1 H )-quinolone, 1-methyl-2-[(Z)-6-undecenyl]-4(1 H )-quinolone, 1-methyl-2-undecyl-4(1 H )-quinolone, evocarpine, 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1 H )-quinolone and dihydroevodiamine) in 15 min and CZE technique was used to determine the dehydroevodiamine in 5 min. Linearity over one order of magnitude of concentration was generally obtained and limits of detection for the alkaloids were in the range of 35–47 μg/ml. The relative standard deviations were less than 4% ( n =6). Contents of Evodiae alkaloids in a methanol-water extract of Evodia fructus sampled could easily be determined by this method. The effects of pH, surfactant concentration and organic modifier concentration of the carrier on the migration behaviour of the solutes are discussed.

The digitalized Instrumentation and Control (I&C) system of nuclear power plants (NPP) could provide operator easily Human-Machine Interface (HMI) and more powerful overall operation capability. However, some software errors may cause a kind of Common Cause Failure (CCF). As a consequence, the event of Anticipated Transients Without Scram (ATWS) will occur. In order to assure that the plant can be shutdown safely and to follow the requirements of 10CFR50.62, the utility builds up various ATWS mitigation features in NPP. The features include Fine Motion Control Rod Drive Run In, Alternate Rod Insertion, Standby Liquid Control System, Reactor Internal Pump Trip or Runback, Feedwater Flow Runback and Inhibition of Automatic Depressurization System. This research developed an evaluation method of diverse back-up means for computerized I&C system. A diverse backup of digital I&C system is the most important means to defend against CCF and un-detectable software faults. Institute of Nuclear Energy Research (INER) is developing a computerized I&C test facility, which is incorporated a commercial grade I&C systems with Personal Computer Transient Analyzer (PCTran)/Advanced Boiling Water Reactor (ABWR), a NPP simulation computer code. By taking the technology of Field Programmable Gate Array (FPGA) to implement the methods of ATWS mitigation, the research built up a diverse back-up of digital I&C system to expect to defend against CCF and undetectable software faults. According to the testing and evaluation, the work can be achieved the analysis of Diversity and Defense-in-Depth (D3).

The ocellar L-neurons of cockroach Periplaneta americana were used in the present study as model systems to investigate the pharmacological properties of the GABA receptors. To do so, a glass microelectrode was impaled into the axon of the L-neurons to record the membrane potential intracellularly and to monitor membrane response to GABA treatment and cercal stimulation by air puff. The traditional GABA and their receptor agonists were introduced through perfusion and/or iontophoresis to monitor their effects on the L-neurons. The GABA receptor antagonists were administered by perfusion to examine if the response of the L-neurons to GABA and/or cercal stimulation was changed. The results revealed that administration of GABA, muscimol and imidazole acetic acid, two GABAA agonists, produced depolarization on the L-neurons. However, treatment of 3-APS and guanidine acetic acid, another two GABAA agonists, evoked hyperpolarization on the L-neurons. Among those tested antagonists, only picrotoxin, GABAA antagonist, antagonize the depolarization induced by GABA and/or cercal stimulation. More interestingly, administration of strychnine, glycine receptor antagonist, largely attenuated the depolarization response of the L-neurons to cercal stimulation. This attenuation caused by strychnine was even stronger than that initiated by varied GABA antagonists. In addition, phaclofen, a GABAB receptor antagonist, showed no antagonistic effect. These results strongly suggest that the characteristics of GABA receptors of the ocellar L-neurons may differ from those in vertebrates. It may be more likely to be a novel GABA receptor.

Recent research has proposed several low-power design techniques for VLSI circuitry in nano-scale CMOS era. However, these techniques always involve custom layout design or novel EDA flows. In this paper essential low power techniques such as voltage separation, body bias and power switch are implemented in existent place and route (P&R) tools. These techniques enable the possibility to integrated low power techniques into standard Cell-Based physical design flow. The result of these research shows a little overhead in design procedure equally area overhead compare with fully custom design flow. The proposed low power design techniques can be cooperated with modern power management system to enable the power reduction in targeting circuitry with small implementation overheads.

We developed a method to analyze the fingerprint spectrum qualitatively and quantitatively for the traditional Chinese herbal medicinal preparation Gan-Lu-Yin with HPLC combined with photodiode array detection, and MS, and to identify the preparation's 14 main components including baicalin, baicalein, oroxylin A-7-O-glucuronide, wogonin-7-O-glucuronide, wogonin, and oroxylin A in Radix Scutellariae; naringin and neohesperidin in Aurantii fructus; liquiritigenin, liquiritin, and glycyrrhizic acid in Radix Glycyrrhizae. In LC/UV assay, a Cosmosil 5C18-MS-II column was used as the stationary phase, and a gradient of potassium dihydrogen phosphate, ACN, and water as the elute solution. The UV detection wavelengths were 250 and 280 nm. In LC/MS assay, a gradient of phosphoric acid, ACN, and water was used as the elute solution, and electrospray positive ion mode ((+)-ESI) as the analytic mode. In order to explore the distribution of trace metal elements effectively in Gan-Lu-Yin, a microwave digestion method was used for sample treatment, and an inductively coupled plasma MS assay was used to analyze fingerprint spectra of the inorganic metals in Gan-Lu-Yin. Combined with fingerprint spectra of organic compounds by LC/UV and LC/MS, it was expected to provide effective quality control in the production of Gan-Lu-Yin.