A combination of isoliquiritigenin with Artemisia argyi and Ohwia caudata water extracts attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/Ho-1 signaling pathways in SD rats with doxorubicin-induced acute cardiotoxicity.

Ohwia caudata (Thunb.) H. Ohashi (Leguminosae) also called as "Evergreen shrub" and Artemisia argyi H.Lév. and Vaniot (Compositae) also named as "Chinese mugwort" those two-leaf extracts frequently used as herbal medicine, especially in south east Asia and eastern Asia. Anthracyclines such as doxorubicin (DOX) are commonly used as effective chemotherapeutic drugs in anticancer therapy around the world. However, chemotherapy-induced cardiotoxicity, dilated cardiomyopathy, and congestive heart failure are seen in patients who receive DOX therapy, with the mechanisms underlying DOX-induced cardiac toxicity remaining unclear. Mitochondrial dysfunction, oxidative stress, inflammatory response, and cardiomyocytes have been shown to play crucial roles in DOX-induced cardiotoxicity. Isoliquiritigenin (ISL, 10 mg/kg) is a bioactive flavonoid compound with protective effects against inflammation, neurodegeneration, cancer, and diabetes. Here, in this study, our aim is to find out the Artemisia argyi (AA) and Ohwia caudata (OC) leaf extract combination with Isoliquiritigenin in potentiating and complementing effect against chemo drug side effect to ameliorate cardiac damage and improve the cardiac function. In this study, we showed that a combination of low (AA 300 mg/kg; OC 100 mg/kg) and high-dose(AA 600 mg/kg; OC 300 mg/kg) AA and OC water extract with ISL activated the cell survival-related AKT/PI3K signaling pathway in DOX-treated cardiac tissue leading to the upregulation of the antioxidant markers SOD, HO-1, and Keap-1 and regulated mitochondrial dysfunction through the Nrf2 signaling pathway. Moreover, the water extract of AA and OC with ISL inhibited the inflammatory response genes IL-6 and IL-1ß, possibly through the NFκB/AKT/PI3K/p38α/NRLP3 signaling pathways. The water extract of AA and OC with ISL could be a potential herbal drug treatment for cardiac hypertrophy, inflammatory disease, and apoptosis, which can lead to sudden heart failure.

Human adipose-derived stem cells preconditioned with a novel herbal formulation Jing Shi attenuate doxorubicin-induced cardiac damage.

Pathological cardiac hypertrophy is a considerable contributor to global disease burden. Chinese herbal medicine (CHM) has been used to treat cardiovascular diseases since antiquity. Enhancing stem cell-mediated recovery through CHM represents a promising approach for protection against doxorubicin (Dox)-induced cardiac hypertrophy. Herein, we investigated whether human adipose-derived stem cells (hADSCs) preconditioned with novel herbal formulation Jing Si (JS) improved protective ability of stem cells against doxorubicin-induced cardiac damage. The effect of JS on hADSC viability and migration capacity was determined via MTT and migration assays, respectively. Co-culture of hADSC or JS-preconditioned hADSCs with H9c2 cells was analyzed with immunoblot, flow cytometry, TUNEL staining, LC3B staining, F-actin staining, and MitoSOX staining. The in vivo study was performed M-mode echocardiography after the treatment of JS and JS-preconditioned hADSCs by using Sprague Dawley (SD) rats. Our results indicated that JS at doses below 100 µg/mL had less cytotoxicity in hADSC and JS-preconditioned hADSCs exhibited better migration. Our results also revealed that DOX enhanced apoptosis, cardiac hypertrophy, and mitochondrial reactive oxygen species in DOX-challenged H9c2 cells, while H9c2 cells co-cultured with JS-preconditioned hADSCs alleviated these effects. It also enhanced the expression of autophagy marker LC3B, mTOR and CHIP in DOX-challenged H9c2 cells after co-culture with JS-preconditioned hADSCs. In Dox-challenged rats, the ejection fraction and fractional shortening improved in DOX-challenged SD rats exposed to JS-preconditioned hADSCs. Taken together, our data indicate that JS-preconditioned stem cells exhibit a cardioprotective capacity both in vitro and in vivo, highlighting the value of this therapeutic approach for regenerative therapy.

Protective effects of Scoparia dulcis L. extract on high glucose-induced injury in human retinal pigment epithelial cells.

Diabetic retinopathy (DR) is a major cause of vision loss in diabetic patients. Hyperglycemia-induced oxidative stress and the accumulation of inflammatory factors result in blood-retinal barrier dysfunction and the pathogenesis of DR. Scoparia dulcis L. extract (SDE), a traditional Chinese medicine, has been recently recognized for its various pharmacological effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory, and anti-oxidative activities. However, there is no relevant research on the protective effect of SDE in DR. In this study, we treated high glucose (50 mM) in human retinal epithelial cells (ARPE-19) with different concentrations of SDE and analyzed cell viability, apoptosis, and ROS production. Moreover, we analyzed the expression of Akt, Nrf2, catalase, and HO-1, which showed that SDE dose-dependently reduced ROS production and attenuated ARPE-19 cell apoptosis in a high-glucose environment. Briefly, we demonstrated that SDE exhibited an anti-oxidative and anti-inflammatory ability in protecting retinal cells from high-glucose (HG) treatment. Moreover, we also investigated the involvement of the Akt/Nrf2/HO-1 pathway in SDE-mediated protective effects. The results suggest SDE as a nutritional supplement that could benefit patients with DR.

Recuperative herbal formula Jing Si maintains vasculature permeability balance, regulates inflammation and assuages concomitants of "Long-Covid".

Coronavirus disease 2019 (COVID-19) is a worldwide health threat that has long-term effects on the patients and there is currently no efficient cure prescribed for the treatment and the prolonging effects. Traditional Chinese medicines (TCMs) have been reported to exert therapeutic effect against COVID-19. In this study, the therapeutic effects of Jing Si herbal tea (JSHT) against COVID-19 infection and associated long-term effects were evaluated in different in vitro and in vivo models. The anti-inflammatory effects of JSHT were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in Omicron pseudotyped virus-induced acute lung injury model. The effect of JSHT on cellular stress was determined in HK-2 proximal tubular cells and H9c2 cardiomyoblasts. The therapeutic benefits of JSHT on anhedonia and depression symptoms associated with long COVID were evaluated in mice models for unpredictable chronic mild stress (UCMS). JSHT inhibited the NF-ƙB activities, and significantly reduced LPS-induced expression of TNFα, COX-2, NLRP3 inflammasome, and HMGB1. JSHT was also found to significantly suppress the production of NO by reducing iNOS expression in LPS-stimulated RAW 264.7 cells. Further, the protective effects of JSHT on lung tissue were confirmed based on mitigation of lung injury, repression in TMRRSS2 and HMGB-1 expression and reduction of cytokine storm in the Omicron pseudotyped virus-induced acute lung injury model. JSHT treatment in UCMS models also relieved chronic stress and combated depression symptoms. The results therefore show that JSHT attenuates the cytokine storm by repressing NF-κB cascades and provides the protective functions against symptoms associated with long COVID-19 infection.

Using radial pulse wave as hemodynamic measurements to quantify effects of acupuncture therapy for patients with traumatic brain injury and ischemia stroke.

Background and aim: Traumatic Brain Injury (TBI) and stroke are major sources of death and disability worldwide. Acupuncture has been used as a supplemental therapy for patients with TBI and stroke. This study was aimed to evaluate the effects of acupuncture therapy for patients with TBI and stroke by radial pulse spectrum. Experimental procedure: 22 patients (6 TBI and 16 stroke) were enrolled and underwent radial pressure wave measurement before and after acupuncture treatment at Dubi (ST-35), Zusanli (ST-36) and Jiexi (ST-41). The harmonic analysis of the radial pressure wave was calculated and transformed into Fourier series coefficients Cn, Pn and the variation coefficient CnCV. Results: After acupuncture, systolic blood pressure, heart rate, and Glasgow Coma Scale changed very slightly. The harmonic index C4, C7, C9, C10, C3CV and C5CV had significant increases. (P < 0.05) After 3-week course acupuncture treatment, systolic blood pressure, C7, C8, C9, C10 and P10 had significant increases. (P < 0.05). Conclusion: Harmonic analysis of radial pulse waves may detect earlier circulatory system changes of acupuncture treatment before they were evident with other hemodynamic readings or scale.

Combined effect of traditional Chinese herbal-based formulations Jing Si herbal tea and Jing Si nasal drop inhibits adhesion and transmission of SARS-CoV2 in diabetic SKH-1 mice.

Multiple studies show increased severity of SARS-CoV2-infection in patients with comorbidities such as hypertension and diabetes. In this study, we have prepared two herbal-based formulations, a pleiotropic herbal drink (Jin Si Herbal Tea, JHT) and a nasal drop (Jin Si nasal drop, JND), to provide preventive care against SARS-CoV2 infection. The effect of JHT and JND was determined in SARS-CoV2-S-pseudotyped lentivirus-infected bronchial and colorectal cell lines and in SKH-1 mouse models. For preliminary studies, ACE2 receptor abundant bronchial (Calu-3) and colorectal cells (Caco-2) were used to determine the effect of JHT and JND on the host entry of various variants of SARS-CoV2-S-pseudotyped lentivirus. A series of experiments were performed to understand the infection rate in SKH-1 mice (6 weeks old, n = 9), find the effective dosage of JHT and JND, and determine the combination effect of JHT and JND on the entry and adhesion of various variant SARS-CoV2-S-pseudotyped lentiviruses, which included highly transmissible delta and gamma mutants. Furthermore, the effect of combined JHT and JND was determined on diabetes-induced SKH-1 mice against the comorbidity-associated intense viral entry and accumulation. In addition, the effect of combined JHT and JND administration on viral transmission from infected SKH-1 mice to uninfected cage mate mice was determined. The results showed that both JHT and JND were effective in alleviating the viral entry and accumulation in the thorax and the abdominal area. While JHT showed a dose-dependent decrease in the viral load, JND showed early inhibition of viral entry from day 1 of the infection. Combined administration of 48.66 mg of JHT and 20 µL of JND showed rapid reduction in the viral entry and reduced the viral load (97-99%) in the infected mice within 3 days of treatment. Moreover, 16.22 mg of JHT and 20 µL JND reduced the viral infection in STZ-induced diabetic SKH-1 mice. Interestingly, combined JHT and JND also inhibited viral transmission among cage mates. The results, therefore, showed that combined administration of JHT and JND is a novel and an efficient strategy to potentially prevent SARS-CoV2 infection.

Clinical course of patients with severe SARS-CoV-2 infection co-treatment with Jin Si Herbal Tea in Eastern Taiwan: A retrospective cohort study.

Introduction: Coronavirus disease-2019 (COVID-19) has affected more than 608 million people and has killed 6.5 million people in the world. A few studies showed traditional Chinese medicine can be beneficial for COVID-19 treatment. An herbal preparation Jin Si Herbal Tea (JS) was formulated with herbal extracts known for their potential to decrease spike protein and ACE2 interaction, 3CL, and TRPMSS2 protease activity, and thus aimed to evaluate the clinical course of JS co-treatment along with the usual treatment schedule given for severe COVID-19 patients. Methods: This retrospective cohort study included patients with severe COVID-19 admitted to Hualien Tzu Chi Hospital between June and July 2021. All the patients were co-treated with JS and the primary outcome was death. The secondary outcomes included laboratory exam, Ct value, clinical course, and hospital stays. There were 10 patients recruited in this study and divided into < 70 years and ≧ 70 years groups (n = 5 in each group). Results: Older patients (≧70 years) had a higher Charlson Comorbidity Index, VACO index, and lower hemoglobin levels than < 70 years patients. The trend of lymphocyte count, LDH, D-dimer, and Ct value of non-survivors was not consistent with previous studies. The death rate was 20% and the recovery rate to mild illness in 14 days was 40%. Conclusion: In conclusion, this is the first clinical study of JS co-treatment in severe COVID-19 patients. JS co-treatment might reduce death rate and recovery time. Further large-scale clinical trials would be expected.

Artemisia argyi extract induces apoptosis in human gemcitabine-resistant lung cancer cells via the PI3K/MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi H. Lév. & Vaniot (Asteraceae), also called "Chinese mugwort", is frequently used as a herbal medicine in China, Japan, Korea, and eastern parts of Russia. It is known as "ai ye" in China and "Gaiyou" in Japan. In ancient China, the buds and leaves of A. argyi were commonly consumed before and after Tomb-sweeping Day. It is used to treat malaria, hepatitis, cancer, inflammatory diseases, asthma, irregular menstrual cycle, sinusitis, and pathologic conditions of the kidney and liver. Although A. argyi extract (AAE) has shown anti-tumor activity against various cancers, the therapeutic effect and molecular mechanism of AAE remains to be further studied in lung cancer. AIM OF THE STUDY: This study aimed to demonstrate the anti-tumor effect of AAE and its associated biological mechanisms in CL1-0 parent and gemcitabine-resistant (CL1-0-GR) lung cancer cells. EXPERIMENTAL PROCEDURE: Human lung cancer cells CL1-0 and CL1-0-GR cells were treated with AAE. Cell viability was assessed using the MTT, colony, and spheroid formation assays. Migration, invasion, and immunofluorescence staining were used to determine the extent of epithelial- mesenchymal transition (EMT). JC-1 and MitoSOX fluorescent assays were performed to investigate the effect of AAE on mitochondria. Apoptosis was detected using the TUNEL assay and flow cytometry with Annexin V staining. RESULT: We found that A. argyi significantly decreased cell viability and induced apoptosis, accompanied by mitochondrial membrane depolarization and increased ROS levels in both parent cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0-GR). AAE-induced apoptosis is regulated via the PI3K/AKT and MAPK signaling pathways. It also prevents CL1-0 and CL1-0-GR cancer cell invasion, migration, EMT, colony formation, and spheroid formation. In addition, AAE acts cooperative with commercial chemotherapy drugs to enhance tumor spheroid shrinkage. CONCLUSION: Our study provides the first evidence that A. argyi treatment suppresses both parent and gemcitabine-resistant lung cancer cells by inducing ROS, mitochondrial membrane depolarization, and apoptosis, and reducing EMT. Our finding provides insights into the anti-cancer activity of A. argyi and suggests that A. argyi may serve as a chemotherapy adjuvant that potentiates the efficacy of chemotherapeutic agents.

Artemisia argyi extract ameliorates IL-17A-induced inflammatory response by regulation of NF-κB and Nrf2 expression in HIG-82 synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that results in joint destruction and disability in the adult population. RA is characterized by the accumulation and proliferation of fibroblast-like synoviocytes. Many pro-inflammatory mediators are associated with RA, such as interleukin (IL)-1ß, IL-6, IL-17, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB). Furthermore, IL-17 upregulates the production of other pro-inflammatory mediators, including IL-1ß and IL-6, and promotes the recruitment of neutrophils in RA. Artemisia argyi, a traditional Chinese herbal medicine, is used for the treatment of diseases associated with inflammation and microbial infections. In this study, synoviocytes (HIG-82) were treated with varying doses of A. argyi extract (AAE) following IL-17A stimulation. Proliferation of the IL-17A-stimulated cells was increased compared to that of the non-stimulated control cells. However, cell proliferation decreased significantly in a dose-dependent manner following AAE treatment. Treatment of IL-17A-stimulated cells with AAE resulted in decreased levels of phosphorylated (p)-NF-κB, p-IκB-α, and COX-2. Enzyme-linked immunosorbent assay results showed that IL-1ß and IL-6 levels were increased in the IL-17A-stimulated group but decreased in the AAE treatment group. Additionally, we found that AAE facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of heme oxygenase-1. Moreover, AAE did not attenuate IL-17A-induced inflammatory mediator production in the presence of ML385, an Nrf2-specific inhibitor. These results suggest that the downregulation of expression of pro-inflammatory cytokines and the transcription factor NF-κB by AAE may be a potential therapeutic strategy for reducing inflammation associated with RA.

Artemisia argyi exhibits anti-aging effects through decreasing the senescence in aging stem cells.

Aging is accompanied by functional loss of many cellular pathways, creating an increased risk of many age-related complications (ARC). Aging causes stem cell exhaustion with a concomitant increase in cellular dysfunction. Recently, interest in senotherapeutics has been growing rapidly to promote healthy aging and as an intervention for ARCs. This research focused on screening the senomorphic properties of Artemisia argyi, as an emerging strategy for longevity, and prevention or treatment of ARCs. In this study, we aimed to find the clinical efficacy of daily consumption of Artemisia argyi water extract (AAW) on aging. In vitro 0.1µM Doxorubicin induced senescent human adipose derived mesenchymal stem cells was treated with different concentrations of AAW to show its anti-aging effect. 15 months old SHR rats (n=6) were treated with 7.9 mg/ml AAW for 4 weeks and anti-aging effect was evaluated. In vitro study showed the protective effect of AAW in telomere shortening and helps in maintaining a balance in the expression of anti-aging protein Klotho and TERT. AAW effectively reduced mitochondrial superoxide and also provided a protective shield against senescence markers like over-expression of p21 and formation of double strand breaks, which is known to cause premature aging. Moreover, animal studies indicated that AAW promoted the expression of Klotho in naturally aging rats. In addition, AAW successfully restored the decline cardiac function and improved the grip strength and memory of aging rat. These findings showed that therapeutic targeting of senescent stem cells by AAW restored stem cell homeostasis and improves overall health.

Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder involving the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Cellular clearance mechanisms, including the autophagy-lysosome pathway, are commonly affected in the pathogenesis of PD. The lysosomal Ca2+ channel mucolipin TRP channel 1 (TRPML1) is one of the most important proteins involved in the regulation of autophagy. Artemisia argyi Lev. et Vant., is a traditional Chinese herb, that has diverse therapeutic properties and is used to treat patients with skin diseases and oral ulcers. However, the neuroprotective effects of A. argyi are not explored yet. HYPOTHESIS: This study aims is to investigate the neuroprotective effects of A. argyi in promoting the TRPML1-mediated autophagy/mitophagy-enhancing effect METHODS: In this study, we used 1-methyl-4-phenyl-pyridinium (MPP+)-induced PD model established in an SH-SY5Y human neuroblastoma cell line as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice. MTT assay was conducted to measure the cell viability and further MitoSoX and DCFDA assay were used to measure the ROS. Western blot analysis was used to access levels of TRPML1, p-DRP1 (ser616), p-AKT, PI3K, and ß-catenin, Additionally, IF and IHC analysis to investigate the expression of TRPML1, LC3B, ß-catenin, TH+, α-synuclein. Mitotracker stain was used to check mitophagy levels and a lysosomal intracellular activity kit was used to measure the lysosomal dysfunction. Behavioral studies were conducted by rotarod and grip strength experiments to check motor functions. RESULTS: In our in vitro study, A. argyi rescued the MPP+-induced loss of cell viability and reduced the accumulation of mitochondrial and total reactive oxygen species (ROS). Subsequently, it increased the expression of TRPML1 protein, thereby inducing autophagy, which facilitated the clearance of toxic accumulation of α-synuclein. Furthermore, A. argyi played a neuroprotective role by activating the PI3K/AKT/ß-catenin cell survival pathway. MPP+-mediated mitochondrial damage was overcome by upregulation of mitophagy and downregulation of the mitochondrial fission regulator p-DRP1 (ser616) in SH-SY5Y cells. In the in vivo study, A. argyi ameliorated impaired motor function and rescued TH+ neurons in the SNpc region. Similar to the results of the in vitro study, TRPML1, LC3B, and ß-catenin expression was enhanced in the SNpc region in the A. argyi-treated mice brain. CONCLUSION: Thus, our results first demonstrate that A. argyi can exert neuroprotective effects by stimulating TRPML1 and rescuing neuronal cells by boosting autophagy/mitophagy and upregulating a survival pathway, suggesting that A. argyi can further be exploited to slow the progression of PD.

Efficacy of Acupuncture Treatment for Incidence of Poststroke Comorbidities: A Systematic Review and Meta-Analysis of Nationalized Cohort Studies.

Acupuncture has been applied as a complementary therapy in stroke survivors worldwide and approved to be beneficial to stroke recovery. However, there is little medical evidence regarding the association between acupuncture and the risk of poststroke comorbidities. We reviewed big data studies from the Taiwan National Health Insurance Research Database to investigate the risk of poststroke comorbidities after acupuncture treatment in a real-world situation. Ten English (PubMed, Embase, Medline, Cochrane, Alt HealthWatch, CINAHL, Health Source, PsycINFO, PsycARTICLES, and Psychology and Behavioral Sciences Collection) and two Chinese (AiritiLibray and Visualizing Health Data) electronic databases were searched from inception until December 2020 for nationalized cohort studies comparing the effects of acupuncture treatment with a nonacupuncture control group among stroke patients. Eight nationalized cohort studies were included. Six of eight studies showed a moderate overall risk of bias, while two studies showed a serious overall risk of bias. Included studies have investigated the effect of acupuncture in reducing the risk of seven medical conditions after stroke, including stroke recurrence, new-onset acute myocardial infarction (AMI), pneumonia, dementia, epilepsy, urinary tract infection (UTI), and depression. The meta-analysis showed clinically significant reductions in the risk of poststroke comorbidities in the acupuncture group compared to the nonacupuncture group (HR, 0.776; 95% CI, 0.719-0.838; p < 0.0001). In this systematic review and meta-analysis of nationalized cohort studies, acupuncture showed clinically relevant benefits in reducing the incidence of poststroke comorbidities, such as stroke recurrence, new-onset acute myocardial infarction (AMI), pneumonia, dementia, epilepsy, and UTI.

Novel anti-aging herbal formulation Jing Si displays pleiotropic effects against aging associated disorders.

Common characteristics of aging include reduced somatic stem cell number, susceptibility to cardiac injuries, metabolic imbalances and increased risk for oncogenesis. In this study, Pleiotropic anti-aging effects of a decoction Jing Si herbal drink (JS) containing eight Traditional Chinese Medicine based herbs, with known effects against aging related disorders was evaluated. Adipose derived mesenchymal stem cells (ADMSCs) from 16 week old adult and 24 month old aging WKY rats were evaluated for the age-related changes in stem cell homeostasis. Effects of JS on self-renewal, klotho and Telomerase Reverse Transcriptase expression DNA damage response were determined by immunofluorescence staining. The effects were confirmed in senescence induced human ADMSCs and in addition, the potential of JS to maintain telomere length was evaluated by qPCR analysis in ADMSCs challenged for long term with doxorubicin. Further, the effects of JS on doxorubicin-induced hypertrophic effect and DNA damage in H9c2 cardiac cells; MPP+-induced damages in SH-SY5Y neuron cells were investigated. In addition, effects of JS in maintaining metabolic regulation, in terms of blood glucose regulation in type-II diabetes mice model, and their potential to suppress malignancy in different cancer cells were ascertained. The results show that JS maintains stem cell homeostasis and provides cytoprotection. In addition JS regulates blood glucose metabolism, enhances autophagic clearances in neurons and suppresses cancer growth and migration. The results show that JS acts on multiple targets and provides a cumulative protective effect against various age-associated disorders and therefore it is a candidate pleiotropic agent for healthy aging.

3-N-butylphthalide protects against high-fat-diet-induced obesity in C57BL/6 mice and increases metabolism in lipid-accumulating cells.

Obesity is one of the world's largest health problems, and 3-N-butylphthalide (NBP), a bioactive compound in celery, has been used in dieting and weight management programs. In this study, NBP prevented high-fat-diet-induced weight gain, reduced the food efficiency ratio, altered the blood biochemical profile, and reduced the obesity-related index. NBP reduced adiposity, white fat depots, liver weight, and hepatic steatosis in obese mice. NBP ameliorated the diabetic state by decreasing glucose levels and improving glucose and insulin tolerance. NBP increased uncoupling protein-1 expression in white adipose tissue and upregulated thermogenesis by enhancing mitochondrial respiration. NBP inhibited white adipocyte development by prohibiting lipid accumulation in human adipose-derived stem cells. NBP increased free fatty acid uptake and the oxygen consumption rate in beige adipocytes. Our results suggest that NBP could be used as functional natural supplement against obesity and its associated disorders.

Chinese herbs and acupuncture to improve cognitive function in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease with a variety of causes. Traditional Chinese medicine (TCM), which includes the two main approaches of acupuncture and herbal medication, views the human body as a self-controlled system network. Fundamental theories, including "qi," the five elements, and the theory of viscera, form the basis for classification. Diseases in humans are considered to be caused by an imbalance of "yang qi" and "yin qi" that lead to the nonhomeostasis of organs. Acupuncture is derived from 12 main meridians and 365 acupuncture points characterized by "blood and qi." Needling of different positions corresponds to specific disease treatments to increase qi. Treatment with Chinese herbal medicines is based on syndrome differentiation characterized as "Zheng" which differs from the cause orientation approach of Western medicine. In this article, we review basic and clinical research studies that describe TCM herbs and acupuncture for the treatment of AD. Moreover, we propose that these two approaches be integrated to improve the outcomes for AD patients.

Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial.

BACKGROUND: Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life. METHODS: For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005. FINDINGS: Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred. INTERPRETATION: Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing. FUNDING: National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.

First insights on value-based healthcare of elders using ICHOM older person standard set reporting.

BACKGROUND: Clinical guidelines for specific conditions fragment care provision for elders. The International Consortium for Health Outcomes Measurement (ICHOM) has developed a global standard set of outcome measures for comprehensive assessment of older persons. The goal of this study was to report value-based health metrics in Taiwan using this ICHOM toolset. METHODS: The cross-sectional study of baseline data excerpted from a prospective longitudinal cohort, which recruited people ≥65 years old with ≥3 chronic medical conditions between July and December 2018. All participants received measurements of physical performance, anthropometric characteristics, health-related behaviors, Charlson Comorbidity Index, and Montreal Cognitive Assessment. The ICHOM toolset comprises three tiers: 1 includes frailty and having chosen a preferred place of death; 2 includes polypharmacy, falls, and participation in decision-making; and 3 includes loneliness, activities of daily living, pain, depression, and walking speed. These items were converted into a 0-10 point value-based healthcare score, with high value-based health status defined as ≥8/10 points. RESULTS: Frequencies of individual ICHOM indicators were: frail 11.7%, chose preferred place of death 14.4%, polypharmacy 31.5%, fell 17.1%, participated in decision-making 81.6%, loneliness 26.8%, limited activities of daily living 22.4%, pain 10.4%, depressed mood 13.0%, and slowness 38.5%. People with high disease burden (OR 0.40, 95% CI 0.21-0.76, p = 0.005) or cognitive impairment (OR 0.49, 95%CI 0.27-0.87, p = 0.014) were less likely to have high value-based healthcare status. CONCLUSIONS: The ICHOM Standard Set Older Person health outcome measures provide an opportunity to shift from a disease-centric medical paradigm to whole person-focused goals. This study identified advanced age, chronic disease burden and cognitive impairment as important barriers to achieving high value-based healthcare status.

Induced Pluripotent Stem Cell (iPSC)-Based Neurodegenerative Disease Models for Phenotype Recapitulation and Drug Screening.

Neurodegenerative diseases represent a significant unmet medical need in our aging society. There are no effective treatments for most of these diseases, and we know comparatively little regarding pathogenic mechanisms. Among the challenges faced by those involved in developing therapeutic drugs for neurodegenerative diseases, the syndromes are often complex, and small animal models do not fully recapitulate the unique features of the human nervous system. Human induced pluripotent stem cells (iPSCs) are a novel technology that ideally would permit us to generate neuronal cells from individual patients, thereby eliminating the problem of species-specificity inherent when using animal models. Specific phenotypes of iPSC-derived cells may permit researchers to identify sub-types and to distinguish among unique clusters and groups. Recently, iPSCs were used for drug screening and testing for neurologic disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), spinocerebellar atrophy (SCA), and Zika virus infection. However, there remain many challenges still ahead, including how one might effectively recapitulate sporadic disease phenotypes and the selection of ideal phenotypes and for large-scale drug screening. Fortunately, quite a few novel strategies have been developed that might be combined with an iPSC-based model to solve these challenges, including organoid technology, single-cell RNA sequencing, genome editing, and deep learning artificial intelligence. Here, we will review current applications and potential future directions for iPSC-based neurodegenerative disease models for critical drug screening.

Hysterectomy and unilateral salpingectomy associate with a higher risk of subsequent ovarian cancer: A population-based cohort study in Taiwan.

Studies on the relationship between gynecologic surgery and subsequent ovarian cancer have been carried out in limited Western ethnic groups. We aim to evaluate whether receiving hysterectomy and/or salpingectomy associated with ovarian cancer risk in Taiwan.From the Taiwan National Health Insurance Research Database, we identified a gynecologic surgery cohort consisting of women who had newly received hysterectomy (N = 181,151), salpingectomy (N = 45,410) or both hysterectomy and salpingectomy (N = 11,875) in 2000 to 2013. A comparison cohort of 953,744 women was randomly selected from women without the surgeries, frequency-matched by age and index date of the surgery case. They were followed up to identify subsequent ovarian cancer by the end of 2013.The overall ovarian cancer incidence was 4.4-fold greater in the gynecologic surgery cohort than in the comparison cohort (41.5 vs 9.43 per 10 person-years) with an adjusted hazard ratio of 3.86 (95% confidence interval = 2.56-5.84). Women with both hysterectomy and salpingectomy had the highest incidence and followed by women with hysterectomy or salpingectomy (52.5, 45.5, or 23.3 per 10 person-years, respectively). No ovarian cancer was noted in the subgroup with bilateral salpingectomies.We conclude that women with gynecologic surgery of hysterectomy and/or salpingectomy are at an increased risk of developing ovarian cancer, particularly among women who have had other gynecologic comorbidity. Women with gynecologic surgery and comorbidity deserve greater attention to prevent and screen for ovarian cancer.

Epigenetic targeting DNMT1 of pancreatic ductal adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through hedgehog pathway inhibition.

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug. n-BP could inhibit DNMT1 expression in both dose-dependent and time-dependent manner. It also displays an effect in suppressing growth of PDAC cells and inducing cell cycle arrest at G0/G1 phase leading apoptosis. Growth suppression can be restored by the overexpression of DNMT1 in PDAC cells. Furthermore, we found n-BP-mediated DNMT1 suppression influenced the protein stability rather than changing the RNA expression. Through microarray studies, we found that the patched domain contained 4 (PTCHD4) is the potential downstream gene of DNMT1. Following silencing of PTCHD4 expression by siRNA, n-BP decreased tumor growth inhibition. Finally, in vivo, two animal models were used to evaluate the efficacy and survival after n-BP treatment by interstitial control release polymer delivery. The results show that n-BP could effectively inhibit PDAC tumor volume growth and extend animal survival. In summary, n-BP may inhibit the growth of human PDAC cells though reducing DNMT1 and increasing the expression of PTCHD4 both in vitro and in vivo.