Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus.

Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we investigated the impact of an ethanolic extract of Melia toosendan fructus (MTE) on osteoclast differentiation and characterized its principal active constituent in osteoclast differentiation and function, as well as its effects on bone protection. Our findings demonstrate that MTE effectively inhibits the differentiation of osteoclast precursors induced by receptor activator of nuclear factor κB ligand (RANKL). Utilizing a bioassay-guided fractionation approach coupled with UHPLC-MS/MS analysis, we isolated and identified the triterpenoid compound toosendanin (TSN) as the active constituent responsible for MTE's anti-osteoclastogenic activity. TSN treatment downregulated the expression of nuclear factor of activated T cells c1, a pivotal osteoclastogenic transcription factor, along with molecules implicated in osteoclast-mediated bone resorption, including tumor necrosis factor receptor-associated factor 6, carbonic anhydrase II, integrin beta-3, and cathepsin K. Furthermore, treatment of mature osteoclasts with TSN impaired actin ring formation, acidification, and resorptive function. Consistent with our in vitro findings, TSN administration mitigated trabecular bone loss and reduced serum levels of the bone resorption marker, C-terminal cross-linked telopeptides of type I collagen, in a mouse bone loss model induced by intraperitoneal injections of RANKL. These results suggest that TSN, as the principal active constituent of MTE with inhibitory effects on osteoclastogenesis, exhibits bone-protective properties by suppressing both osteoclast differentiation and function. These findings imply the potential utility of TSN in the treatment of diseases characterized by excessive bone resorption.

Euonymus alatus (Thunb.) Siebold Prevents Osteoclast Differentiation and Osteoporosis.

Euonymus alatus (Thunb.) Siebold, a traditional medicinal plant, has been used in China and several other Asian countries to address a variety of health concerns. The extensive research conducted on E. alatus is driven by its diverse pharmacological applications. However, its biological effects on osteoclastogenesis and osteoporosis have not been previously studied. In this research, we investigated the impact of an ethanolic extract of E. alatus (EEEA) on osteoclast differentiation and function as well as estrogen deficiency-induced bone loss. We found that EEEA inhibits osteoclast differentiation by downregulating the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoclast-supporting cells and by directly impeding RANKL-mediated signaling pathways for osteoclastogenesis in precursor cells. In addition, EEEA inhibited the bone-resorptive function of mature osteoclasts in vitro. Furthermore, oral administration of EEEA significantly alleviated bone loss in an ovariectomy-induced osteoporosis mouse model. Additionally, we identified phytochemicals in EEEA that have suppressive effects on osteoclast differentiation and bone loss. Collectively, these results suggest that EEEA holds potential as a biotherapeutic candidate for anti-postmenopausal osteoporosis.

Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis.

Background/Aims: Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. Methods: Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models. Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. Results: In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46-2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47-2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32-2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps<0.001). No significant publication bias was observed. Conclusions: Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.

Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.

Waist circumference and end-stage renal disease based on glycaemic status: National Health Insurance Service data 2009-2018.

BACKGROUND: Obesity is associated with an increased risk of developing type 2 diabetes mellitus (T2DM) and end-stage renal disease (ESRD). This study aimed to examine the effect of waist circumference (WC) on the risk for ESRD based on glycaemic status in a Korean population-based sample. METHODS: This cohort study with a 9.2-year follow-up period used a population-based National Health Insurance Service health checkup database with approximately 10 585 852 participants who were followed up from 2009 to the time of ESRD diagnosis. WC was categorized into seven levels in 5-cm increments, with Level 4 as the reference group. Glycaemic status was categorized into the following groups: normal fasting glucose (NFG), impaired fasting glucose (IFG), newly diagnosed T2DM, T2DM treated with ≤2 oral hypoglycaemic agents (OHAs) and diabetes treated with ≥3 OHAs or insulin. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for ESRD according to WC values and glycaemic status of the participants. RESULTS: The study finally included 10 177 245 patients with a mean age of 47.1 (13.8) years. The study population included 5 604 446 men (55.1%) and 4 572 799 women (45.9%). In total, 8.3% (n = 877 143) of the study population had diabetes. During the mean follow-up of 9.2 (1.0) years (93 554 951 person-years of follow-up), 23 031 individuals were newly diagnosed with ESRD. The ESRD risk increased in parallel with an increase in WC in participants without T2DM, that is, the NFG and IFG groups (adjusted HRs [95% CIs] of WC Levels 4, 5 and 6: 1.17 [1.09-1.26], 1.37 [1.25-1.51] and 1.84 [1.63-2.07] in the NFG group and 1.06 [0.97-1.16], 1.23 [1.10-1.38] and 1.80 [1.57-2.06] in the IFG group, respectively). In patients with T2DM, the risk for ESRD was significantly increased in those with a low WC (adjusted HRs [95% CIs] of WC Level 1: 2.23 [1.77-2.80], 3.18 [2.70-3.74] and 10.31 [9.18-11.59] in patients with newly diagnosed diabetes, patients on ≤2 OHAs and those on ≥3 OHAs or insulin, respectively). The association between WC and ESRD thus showed a J-shaped pattern in patients with newly diagnosed T2DM and a U-shaped pattern in those on ≤2 OHAs and on ≥3 OHAs or insulin. CONCLUSIONS: Central obesity substantially increases the risk of developing ESRD regardless of glycaemic status. The harmful effects of low WC only become significant with the progression of T2DM.

Three months-longitudinal changes in relative telomere length, blood chemistries, and self-report questionnaires in meditation practitioners compared to novice individuals during midlife.

Aging accelerates during midlife. Researches have shown the health benefits of mind-body intervention (MBI). However, whether MBI is involved with aging process has not been well understood. In this study, we approach to examine the relations of MBI with this process by investigating an aging marker of the peripheral blood, blood chemistry, and self-report questionnaires. A quasi-experimental design was applied. Experienced MBI practitioners participated in a 3-month intensive meditation training, while the age, gender-matched MBI-naïve controls led a normal daily life. Measurements were taken at before and after the 3 months for relative telomere length (RTL), blood chemistry, and self-report questionnaires including items about sleep quality, somatic symptoms, depression, anxiety, stress, emotional intelligence (EI), and self-regulation. For RTL, the repeated measures analysis of variance showed a significant group*time interaction (P = .013) with a significant post hoc result (P = .030) within the control group: RTL was significantly reduced in the control while it was maintained in the meditation group. In repeated measures analysis of variance for blood chemistries, there were significant group differences between the groups in glucose and total protein. In the post hoc comparison analysis, at post measurements, the meditation group exhibited significantly lower values than the control group in both glucose and total protein. There were significant group-wise differences in the correlations of RTL with triglyceride (TG), high-density lipoprotein (HDL), glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. Any of self-report results did not show significant changes in group*time interaction. However, there were group differences with significant (P < .05) or a tendency (.05 < P < .1) level. There were significant improvements in depression, stress and EI as well as tendencies of improvement in sleep quality and anxiety, in the meditation group compared to the control group. Our results suggest that meditation practice may have a potential to modify aging process in molecular cellular level combined with changes in psychological dimension.

Water Extract of Piper longum Linn Ameliorates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclast Differentiation.

Piper longum linn has traditionally been used for the treatment of respiratory and gastrointestinal disorders in India. Although various pharmacological effects of P. longum have been studied, its effects on bone have not been clearly elucidated. Therefore, this study examined the inhibitory effect of the water extract of P. longum Linn (WEPL) on osteoclast differentiation. WEPL directly affected the osteoclast precursors and suppressed osteoclast differentiation in vitro. In addition, the expression levels of c-Fos and nuclear factor of activated T cells 1, a critical transcription factor for osteoclastogenesis, were significantly downregulated by WEPL via the suppression of the receptor activator of nuclear factor (NF)-κB ligand-induced mitogen-activated protein kinase and NF-κB signaling pathways. Consistent with the in vitro results, oral administration of WEPL (100 and 300 mpk) to ovariectomized mice for six weeks relieved the OVX-induced bone loss. We also identified phytochemicals in WEPL that are reported to exert inhibitory effects on osteoclastogenesis and/or bone loss. Collectively, the findings of our study indicate that WEPL has an anti-osteoporotic effect on OVX-induced bone loss by diminishing osteoclast differentiation, suggesting that it may be useful to treat several bone diseases caused by excessive bone resorption.

The Improvement Effect of D-Chiro-Inositol and Ecklonia cava K. in the Rat Model of Polycystic Ovarian Syndrome.

Introduction: Polycystic Ovarian Syndrome (PCOS) is known to be an endocrine state that is characterized by oligomenorrhea, hyperandrogenism, and highly cystic follicles in the ovaries. The use of food ingredients and traditional medicine in Asian countries is well known, and previous studies have shown that Ecklonia cava K. [Alariaceae] (EC) is able to alleviate PCOS symptoms. D-Chiro-inositol (DCI) administration in pathologies where steroid biosynthesis is a crucial factor, i.e., PCOS, has provided satisfactory results. Methods: Therefore, we studied the synergistic effects of the two previously known active compounds. In rats with letrozole-induced PCOS, we focused on alternative therapies using EC and/or DCI extracts to alleviate ovarian failure. Results: As a nonsteroidal aromatase inhibitor, letrozole inhibits the conversion of testosterone to estrogen and subsequently causes PCOS. We divided 6-week-old female mice into the following six groups and evaluated them: vehicle, PCOS, PCOS + MET (metformin), PCOS + DCI, PCOS + EC, and PCOS + DCI + EC. In our study, PCOS rats treated with EC and DCI had low serum LH and T levels and low serum levels of inflammatory cytokines such as TNFα and IL-6. These treatments also appeared to regulate the production of factors that affect follicle formation and inflammation in the ovaries. Conclusion: We concluded that EC extract and/or DCI administration influenced aromatase production and reduced LH and T stimulation, and cotreatment with EC and DCI consequently restored ovarian dysfunction or anti-inflammatory responses in rats with PCOS-like symptoms.

Utilization of Mind-Body Intervention for Integrative Health Care of COVID-19 Patients and Survivors.

Recent findings suggest a correlation between COVID-19 and diabetes, although the underlying causes are still little understood. COVID-19 infection tends to induce severe symptoms in patients with underlying diabetes, increasing their mortality rate. Moreover, COVID-19 itself appears to be a diabetogenic factor. In addition, mental health conditions, such as depression due to lockdown and anxiety about infection, were found to affect glycemic control and immunity, highlighting the importance of mental health care during the pandemic. Mind-Body Intervention (MBI), which includes meditation, yoga, and qigong, has emerged as a tool for mental health management due to its effects on stress reduction and the promotion of mental and physical well-being. Here, we review the latest randomized controlled trials to determine the effects of MBI on glycemic control and the immune system and discuss the underlying mechanisms by which MBI facilitates the virtuous cycle of stress management, glycemic control, and immune modulation. Furthermore, we examine the actual utilization of MBI during the COVID-19 pandemic era through recent studies. With proper online education, non-pharmacological MBI may be more widely used as an important tool for self-health care that complements the usual treatment of COVID-19 patients and survivors.

Reduced Pain by Mind-Body Intervention Correlates with Improvement of Shoulder Function in People with Shoulder Pain: A Randomized Controlled Trial.

Meditation and acupressure-like stimulations have been shown to relieve pain. The aim of this study was to determine whether a short bout of mind-body intervention combined with meditation and acupressure-like stimulation was able to alleviate shoulder pain and improve its function in a short time window. Sixty-five adults with shoulder pain were recruited and randomly classified into two groups. One group participated in an intervention which consisted of acupressure-like stimulation and meditation over a 5 min period. The other group was instructed to rest during this time. A visual analog scale (VAS) pain score and objective constant scores were measured before and after intervention to determine shoulder pain and range of motion (ROM), respectively. A two-way repeated measures analysis of variance with Bonferroni correction and a regression analysis were performed. VAS pain, objective constant score, flexion, abduction, and external rotation score showed significant interactions between time and group. The pain intensity was significantly reduced, while flexion and abduction were significantly improved, in the experimental group compared to the control group, after the intervention. In addition, the change of flexion negatively correlated with the change of pain intensity in the experimental group, but not in the control group. These results show that a short-term application of mind-body intervention significantly alleviates shoulder pain and improves shoulder movement, suggesting its potential use as a therapy for people with shoulder pain.

Dendropanax trifidus Sap-Mediated Suppression of Obese Mouse Body Weight and the Metabolic Changes Related with Estrogen Receptor Alpha and AMPK-ACC Pathways in Muscle Cells.

Dendropanax trifidus (DT) is a medicinal herb native to East Asia, which has been used extensively for its therapeutic properties in traditional medicine. In this study, we examined the effects of DT sap on the regulation of body weight and muscle metabolism in mice. Obese model db/db mice were administered daily with DT sap or vehicle control over a 6-week period. The effects of DT sap on muscle metabolism were studied in C2C12 muscle cells, where glycolytic and mitochondrial respiration rates were monitored. As AMP-activated protein kinase (AMPK) is a master regulator of metabolism and plays an important function as an energy sensor in muscle tissue, signaling pathways related with AMPK were also examined. We found that DT sap inhibited body weight increase in db/db, db/+, and +/+ mice over a 6-week period, while DT sap-treated muscle cells showed increased muscle metabolism and also increased phosphorylation of AMPK and Acetyl-CoA Carboxylase (ACC). Finally, we found that DT sap, which is enriched in estrogen in our previous study, significantly activates estrogen alpha receptor in a concentration-dependent manner, which can drive the activation of AMPK signaling and may be related to the muscle metabolism and weight changes observed here.

Ethanolic extract of Pyrrosia lingua (Thunb.) Farw. ameliorates OVX-induced bone loss and RANKL-induced osteoclastogenesis.

Pyrrosia lingua (Thunb.) Farw is a common plant that has been widely used as a traditional herbal medicine in China and Korea to treat patients suffering from pain, vaginal bleeding and urolithiasis. However, the pharmacological effects of P. lingua on bone remain unknown. We investigated the anti-osteoporotic effects of an ethanolic extract of P. lingua (EEPL). We found that EEPL suppressed osteoclast differentiation by directly acting on osteoclast precursor cells. EEPL suppressed the expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor of activated T cells 1, a major transcription factor for osteoclastogenesis, by inhibiting RANKL-induced expression of aryl hydrocarbon receptor/c-Fos, and activation of nuclear factor-κB and mitogen-activated protein kinases. Moreover, administration of EEPL inhibited trabecular bone loss and weight gain in ovariectomized mice. Furthermore, we identified phytochemicals in EEPL that are known to exert anti-osteoclastogenic or anti-osteoporotic effects using ultra-high-performance liquid chromatography-tandem mass-spectrometry analysis. Overall, the results of this study suggest that EEPL is effective therapeutic candidate that can be used to prevent or treat postmenopausal osteoporosis.

Weight change and the incidence of heart failure in the Korean population: data from the National Health Insurance Health checkup 2005-2015.

AIMS: Heart failure (HF) is associated with obesity, but the relationship between weight change and HF is inconsistent. We examined the relationship between weight change and the incidence of HF in the Korean population. DESIGN: Retrospective cohort study design. METHODS AND RESULTS: A total of 11 210 394 subjects (6 198 542 men and 5 011 852 women) >20 years of age were enrolled in this study. Weight change over 4 years divided into seven categories from weight loss ≥15% to weight gain ≥15%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of HF were analysed. The HR of HF showed a slightly reverse J-shaped curve by increasing weight change in total and >15% weight loss shows the highest HR (HR 1.647) followed by -15 to -10% weight loss (HR = 1.444). When using normal body mass index with stable weight group as a reference, HR of HF decreased as weight increased in underweight subjects and weight gain ≥15% in obesity Stage II showed the highest HR (HR = 2.97). Sustained weight for 4 years in the underweight and obesity Stages I and II increased the incidence of HF (HR = 1.402, 1.092, and 1.566, respectively). CONCLUSION: Both weight loss and weight gain increased HR for HF. Sustained weight in the obesity or underweight categories increased the incidence of HF.

In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract.

Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components.

Identification and pharmacokinetics of bioavailable anti-resorptive phytochemicals after oral administration of Psoralea corylifolia L.

Osteoporosis and resulting bone fractures are the major health issues associated with morbidity in the aging population; however, there is no effective treatment that does not cause severe side effects. In East Asia, dried seeds of Psoralea corylifolia L. (PC) have traditionally been used as an herbal medicine to manage urinary tract, cutaneous, and gastrointestinal disorders, as well as bone health. However, the mechanism of action and active biocomponents of PC are unclear. Here, we adopted a pharmacokinetic (PK) study aiming to identify the bioavailable phytochemicals in aqueous and ethanolic extracts of PC (APC) and (EPC), respectively. In addition, we aimed to determine anti-resorptive constituents of PC, which accounted for its beneficial effects on bone health. To this end, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A rapid, sensitive, and reliable UPLC-MS/MS method was developed and determined the 17 PC ingredients. In the PK study, nine components (two chalcones, two coumarins, one coumestan, two flavonoids, and two isoflavonoids) were observed between 36 and 48 h after oral administration of APC or EPC. Among the bioavailable ingredients, four PC constituents (psoralidin, isobavachin, corylifol A, and neobavaisoflavone) inhibited M-CSF-and RANKL-induced osteoclast differentiation in bone marrow-derived macrophages. In addition, two chalcones and two isoflavonoids markedly inhibited cathepsin K activity, and their binding modes to cathepsin K were determined by molecular docking. In summary, our data suggest that bioavailable multicomponents of PC could contribute to the management of bone health.

A cross-sectional study on the relationship between meditation training and emotional intelligence in women.

AIM: We aimed to reveal the relationship of meditation with emotional intelligence (EI), sleep quality and melatonin level. DESIGN: A cross-sectional study. METHODS: Our current research was performed on middle-aged women. EI scale, Pittsburgh Sleep Quality Index (PSQI) and night-time saliva melatonin were measured for 65 participants including 33 meditators and 32 controls. RESULTS: The meditation group showed a significantly higher EI score than the control group. In the regression analysis between EI and age, only the meditation group showed a significant positive correlation. The Pearson correlation analysis among all participants revealed a significant negative correlation between PSQI and EI. There was no significant group difference in the melatonin and PSQI.

A Novel Cardenolide Glycoside Isolated from Xysmalobium undulatum Reduces Levels of the Alzheimer's Disease-Associated ß-Amyloid Peptides Aß42 In Vitro.

Elevated levels of the amylo ß-proteins (Aß), particularly Aß42, are associated with a high risk of Alzheimer's disease (AD). The Aß proteins are produced from cellular processing of the amyloid precursor proteins (APPs). To identify natural products that block the formation of Aß-proteins from APPs, we previously screened a library of plant extracts and identified Xysmalobium undulaum (Apocynaceae) as a potential plant for further research. Here, we provide a report on the isolation and identification of the active principles from the plant species using a bioassay-guided fractionation. Fractions and resulting pure compounds from the purification process of the extract of X. undulatum were screened in vitro against APPs transfected HeLa cell lines. Three compounds, acetylated glycosydated crotoxogenin (1), xysmalogenin-3, ß-d-glucopyranoside (2), and crotoxigenin 3-O-glucopyranoside (3), were subsequently isolated and their structures elucidated using NMR and mass spectrometry. Compound 1, a novel cardenolide, and 2 significantly decreased the Aß42 levels in a dose-dependent manner while compound 3 was inactive. In silico investigations identified the AD's ß-secretase enzyme, BACE1, as a potential target for these compounds with the glycoside moiety being of significance in binding to the enzyme active site. Our study provides the first report of a novel cardenolide and the potential of cardenolides as chemical scaffolds for developing AD treatment drugs.

Systematic review and meta-analysis of diagnostic performance of CT imaging for assessing resectability of pancreatic ductal adenocarcinoma after neoadjuvant therapy: importance of CT criteria.

PURPOSE: To assess the CT diagnostic performance for evaluating resectability of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy and identify the factor(s) that affect(s) diagnostic performance. METHODS: Databases were searched to identify studies published from January 1, 2000, to November 5, 2019 that evaluated the CT diagnostic performance for assessing resectability of post-neoadjuvant PDAC. Two reviewers independently extracted data and assessed the study quality. A meta-analysis was performed to obtain summary sensitivity and specificity values using a bivariate random-effects model, and heterogeneity across studies was assessed. Univariable meta-regression analysis was performed with eight variables, including the different CT criteria for resectability, conventional National Comprehensive Cancer Network (NCCN) criteria for upfront surgery, and modified criteria for post-neoadjuvant surgery. RESULTS: Ten studies were included and analyzed. The summary sensitivity and specificity for resectability were 78% (95% CI 68-86%) and 60% (95% CI 44-74%), respectively. No significant heterogeneity was identified (bivariate correlation coefficient ρ = - 1, p-value for hierarchical summary receiver operating characteristics model ß = 0.667). The two different CT criteria showed different diagnostic performance (p < 0.01), with higher sensitivity (81% [95% CI 73-90%] vs. 28% [95% CI 15-42%], p < 0.01) and lower specificity (57% [95% CI 41-73%] vs. 90% [95% CI 80-100%], p < 0.01) for the modified criteria. No other variables affected the diagnostic performance. CONCLUSION: CT criteria were the factors that affected the diagnostic performance. Modification of the conventional criteria improved sensitivity but lowered specificity. Further modifications are required to improve specificity and uniformity.

Susceptibility of Women to Cardiovascular Disease and the Prevention Potential of Mind-Body Intervention by Changes in Neural Circuits and Cardiovascular Physiology.

Women have been reported to be more vulnerable to the development, prognosis and mortality of cardiovascular diseases, yet the understanding of the underlying mechanisms and strategies to overcome them are still relatively undeveloped. Studies show that women's brains are more sensitive to factors affecting mental health such as depression and stress than men's brains. In women, poor mental health increases the risk of cardiovascular disease, and conversely, cardiovascular disease increases the incidence of mental illness such as depression. In connection with mental health and cardiovascular health, the presence of gender differences in brain activation, cortisol secretion, autonomic nervous system, vascular health and inflammatory response has been observed. This connection suggests that strategies to manage women's mental health can contribute to preventing cardiovascular disease. Mind-body interventions, such as meditation, yoga and qigong are forms of exercise that strive to actively manage both mind and body. They can provide beneficial effects on stress reduction and mental health. They are also seen as structurally and functionally changing the brain, as well as affecting cortisol secretion, blood pressure, heart rate variability, immune reactions and reducing menopausal symptoms, thus positively affecting women's cardiovascular health. In this review, we investigate the link between mental health, brain activation, HPA axis, autonomic nervous system, blood pressure and immune system associated with cardiovascular health in women and discuss the effects of mind-body intervention in modulating these factors.