Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example. / 治疗方案临床价值评估在指南制定中的应用.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

Objective and subjective sleep in patients with non-seasonal major depressive disorder and eveningness - Results from a randomized controlled trial of bright light therapy.

STUDY OBJECTIVES: This study examines the (dis)agreement between objective and subjective sleep and their prospective changes in a randomized controlled trial of bright light therapy (BLT) in patients with major depressive disorder (MDD) and eveningness. METHODS: A total of 93 adults were randomized to receive either 30-min daily of 10,000 lux BLT or 50lux placebo dim red light therapy (DRL group) for a total of 5 weeks. Actigraphic data were collected at the baseline and during the last week of treatment. (Dis)Concordance of diary and actigraphic sleep parameters were assessed by partial correlations and Bland-Altman plots, and the associations between these discrepancies to depression severity was assessed by linear regression models. Changes of sleep parameters were assessed by linear mixed models. RESULTS: Significant correlations were found between subjective sleep timings and chronotype to actigraphic parameters. Discrepancies between diary- and actigraphic-measures were observed, and patients with more severe depressive symptoms were associated with a greater under-estimation of total sleep time (TST). A greater advance in the diary-based time to fall sleep and rise time were achieved in the BLT group as compared to the DRL group, while diary-based wake after sleep onset (WASO), TST and sleep efficiency (SE) comparably improved with time in both groups. There was no significant difference between the two groups in the actigraphic parameters after treatment. CONCLUSIONS: In this study, we found that depression severity influenced subjective report of sleep. BLT led to a greater advance in subjective sleep timings when compared to the placebo group.

Tea polyphenols coated sodium alginate-gelatin 3D edible scaffold for cultured meat.

This study aimed to use edible scaffolds as a platform for animal stem cell expansion, thus constructing block-shaped cell culture meat. The tea polyphenols (TP)-coated 3D scaffolds were constructed of sodium alginate (SA) and gelatin (Gel) with good biocompatibility and mechanical support. Initially, the physicochemical properties and mechanical properties of SA-Gel-TP scaffolds were measured, and the biocompatibility of the scaffolds was evaluated by C2C12 cells. SEM results showed that the scaffold had a porous laminar structure with TP particles attached to the surface, while FT-IR results also demonstrated the encapsulation of TP coating on the scaffold. In addition, the porosity of all scaffolds was higher than 40% and the degradation rate during the incubation cycle was less than 40% and the S2-G1-TP0.1-3 h scaffold has excellent cell adhesion and extension. Subsequently, we inoculated rabbit skeletal muscle myoblasts (RbSkMC) on the scaffold and induced differentiation. The results showed good adhesion and extension behavior of RbSkMC on S2-G1-TP0.1-3 h scaffolds with high expression of myogenic differentiation proteins and genes, and SEM results confirmed the formation of myotubes. Additionally, the adhesion rate of cells on scaffolds with TP coating was 1.5 times higher than that on scaffolds without coating, which significantly improved the cell proliferation rate and the morphology of cells with extension on the scaffolds. Furthermore, rabbit-derived cultured meat had similar appearance and textural characteristics to fresh meat. These conclusions indicate the high potential of the scaffolds with TP coating as a platform for the production of cultured meat products.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

Protective effect of hot-water and ethanol-aqueous extracts from Anneslea fragrans against acetaminophen-induced acute liver injury in mice.

Anneslea fragrans Wall. (AF) is an important medicinal and edible plant in China. The principal objectives of this study are to explore the hepatoprotective effect of ethanol-aqueous (AFE) and hot-water (AFW) extracts in vitro and in vivo. UPLC-ESI-MS/MS analysis showed that AFW and AFE are rich in dihydrochalcones. Both AFW and AFE significantly up-regulated the expressions of SOD, CAT and GSH, reduced the MDA content in acetaminophen (APAP)-induced HepG2 cells, and suppressed the expressions of NO, TNF-α, IL-1ß, and IL-6 in LPS-induced RAW246.7 cells. In APAP-induced mice, AFW and AFE administration significantly decreased the plasma levels of AST and ALT, and improved liver tissue damage, the collagen deposition and fibrosis formation. Moreover, AFW and AFE decreased the MDA and ROS accumulations via activating Nrf2 pathway to increase the hepatic GSH contents and activities of SOD, CAT, HO-1, and NQO-1, reduced the levels of NO, TNF-α, IL-1ß, and IL-6 by suppressing the JNK/p38/ERK/NF-κB pathways, and alleviated apoptosis via regulating Bcl-2, Bax, caspase-3/9 protein expressions. This study provides a new sight that AFW and AFE may have a potential natural resource for the treatment of liver injury.

Influence of Ultra-High-Pressure Pretreatment Method on Chemical Constituents, Antioxidant and Cytoprotective Activities of Free, Esterified, and Bound Phenolics from Anneslea Fragrans Wall. Leaves.

Anneslea fragrans Wall., an edible and medicinal plant, is traditionally used to treat liver and gastrointestinal diseases. This paper aimed to investigate the influence of ultra-high pressure (UHP) pretreatment on the phenolics profiling, antioxidant, and cytoprotective activities of free (FP), esterified (EP), and bound (BP) phenolics from A. fragrans leaves. A total of 32 compounds were characterized and quantified. The davidigenin (44.46 and 113.37 mg/g extract) was the highest in A. fragrans leaves. The vitexin (9), afzelin (10), coreopsin (15), and davidigenin (28) were analyzed with MS2 fragment pathways. Results showed that UHP treated A. fragrans leaves had higher total phenolic (TPC) and total flavonoid (TFC) contents of FP, EP, and BP fractions than those in the raw leaves. Moreover, UHP pretreated A. fragrans leaves had higher scavenging activities on DPPH+• and ABTS+•, and inhibitory effects on the intracellular ROS generation in H2O2-induced HepG2 cells. UFP showed the highest inhibition of ROS production among the samples. Therefore, UHP pretreatment method might be used as an effective strategy for elevating the availabilities of A. fragrans leaves to develop functional foods.

E Se tea extract ameliorates CCl4 induced liver fibrosis via regulating Nrf2/NF-κB/TGF-ß1/Smad pathway.

BACKGROUND: Liver fibrosis is a crucial progress to deteriorate liver disease. E Se tea (ES) is an ethnic herbal tea in China that has various biological activities for human beings. However, the traditional application on the treatment of liver disease is not studied. PURPOSE: This study is firstly performed to explore the chemical constituents of ES extract together with its anti-hepatic fibrosis effect and potential mechanism on CCl4 treated mice. STUDY DESIGN AND METHODS: The chemical constituents of ethanol-aqueous extract from ES (ESE) were analyzed by UPLC-ESI-MS/MS. The anti-hepatic fibrosis effect of ESE was determined by measuring ALT and AST activities, antioxidative indexes, inflammatory cytokines and collagen protein levels on CCl4 treated mice. Moreover, H&E, Masson staining and immunohistochemical analysis were performed for evaluating the protective effect of ESE on histopathological changes of liver tissues. RESULTS: UHPLCHRESI-MS/MS analysis showed that the ESE was rich in flavonoids such as phlorizin, phloretin, quercetin and hyperoside. ESE could significantly reduce the plasma AST and ALT activities. The cytokines (IL-6, TNF-α, IL-1ß) expressions were inhibited after ESE administration via suppressing NF-κB pathway. In addition, ESE could decrease MDA accumulation for alleviating CCl4 induced liver oxidative stress via regulating Nrf2 pathway to promote the expressions of antioxidant enzymes (SOD, HO-1, CAT and NQO1). Moreover, ESE could inhibit the expressions of TGF-ß1, Smad2, α-SMA, and collagens Ⅰ and III proteins, thereby effectively alleviate the liver fibrosis. CONCLUSION: This study demonstrated that ESE could alleviate liver fibrosis through enhancing antioxidant and anti-inflammatory abilities by Nrf2/NF-κB pathway and reducing deposition of liver fibrosis via suppressing TGF-ß/Smad pathway.

Protective effect of Anneslea fragrans ethanolic extract against CCl4-induced liver injury by inhibiting inflammatory response, oxidative stress and apoptosis.

Anneslea Fragrans Wall. (AF) is a medicinal and edible plant distributed in China. Its leaves and barks are generally used for the treatments of diarrhea, fever, and liver diseases. While its ethnopharmacological application against liver diseases has not been fully studied. This study was aimed to evaluate the hepatoprotective effect of ethanolic extract from A. fragrans (AFE) on CCl4 induced liver injury in mice. The results showed that AFE could effectively reduce plasma activities of ALT and AST, increase antioxidant enzymes activities (SOD and CAT) and GSH level, and decrease MDA content in CCl4 induced mice. AFE effectively decreased the expressions of inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2 and iNOS), cell apoptosis-related proteins (Bax, caspase-3 and caspase-9) and increased Bcl-2 protein expression via inhibiting MAPK/ERK pathway. Additionally, TUNEL staining, Masson and Sirius red staining, immunohistochemical analyses revealed that AFE could inhibit the CCl4-induced hepatic fibrosis formation via reducing depositions of α-SMA, collagen I and collagen III proteins. Conclusively, the present study demonstrated that AFE had an hepatoprotective effect by suppressing MAPK/ERK pathway to inhibit oxidative stress, inflammatory response and apoptosis in CCl4-induced liver injury mice, suggesting that AFE might be served as a hepatoprotective ingredient in the prevention and treatment of liver injury.

A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activity.

Gardneria distincta P. T. Li is traditionally applied as a herbal medicine for treatment various ailments, and is mainly distributed in Southwestern China. Under the guided separation of MS/MS-based molecular networking, eight undescribed oxindole alkaloids, gardistines A-H, as well as 17 known alkaloids were discovered from the whole parts of Gardneria distincta. Structural elucidation of these undescribed alkaloids was performed by various spectroscopic methods. Gardistine A is a rare oxindole gardneria alkaloid bearing an ester carbonyl group attached to C-18, which is the second reported alkaloid of oxindole gardneria-type. All of the identified monoterpene indole alkaloids were investigated for their anti-inflammatory activity in LPS-induced RAW 264.7 cells. Gardistines A-B and akuammidine demonstrated significant inhibitory effects on the expressions of nitric oxide, tumor necrosis factor alpha, and interleukin-6 at 20 µM.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Effects of Low-Phosphorus Diets Supplemented with Phytase on the Production Performance, Phosphorus-Calcium Metabolism, and Bone Metabolism of Aged Hy-Line Brown Laying Hens.

This study was conducted to evaluate the effects of phytase supplementation in low-phosphorus diets on the production performance, phosphorus-calcium metabolism, and bone metabolism in laying hens from 69 to 78 weeks of age. Hy-Line Brown laying hens (n = 1350) were assigned randomly to six treatments with five replicates of 45 birds. A corn-soybean meal-based diet with no inorganic phosphates was formulated to contain 0.12% non-phytate phosphorus (NPP) and 1470 FTU/kg phytase (Released phytate phosphorus content ≥ 0.1%). Inorganic phosphorus (dicalcium phosphate) was supplemented into the basal diet to construct five test diets (level of NPP supplementation = 0.10%, 0.15%, 0.20%, 0.25%, and 0.30%). The level of calcium carbonate was adjusted to ensure that all six experimental diets contained the same calcium percentage (3.81%). The feeding trial lasted 10 weeks (hens from 69 to 78 weeks of age). Upon supplementation with phytase (1470 FTU/kg), supplemental inorganic phosphates (dicalcium phosphate) had no significant effects (p > 0.05) on the production performance or egg quality. Significant differences in serum levels of calcium, phosphorus, copper, iron, zinc, or manganese were not detected across treatments (p > 0.05). Hens fed NPP (0.15%, 0.20%, 0.25%, and 0.30%) had higher levels (p < 0.0001) of tibial ash, calcium, and phosphorus than those not fed inorganic phosphates. The tibial breaking strength of the group without inorganic phosphates was significantly lower than that of the other groups (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of calcitonin (CT) and 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3). Hens that did not receive supplementation with inorganic phosphates had higher serum levels of parathyroid hormone (PTH), osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) compared with those in the other groups (p < 0.01). Serum levels of CTX-I and TRACP-5b were significantly lower in the NPP-supplementation groups of 0.25% and 0.30% than in the 0.10% NPP-supplementation group (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of bone-alkaline phosphatase (BAP), osteocalcin (OCN), or osteopontin (OPN). Hens not fed inorganic phosphate had the highest renal expression of phosphorus transporter type IIa Na/Pi cotransporter (NaPi-Ⅱa). Renal expression of NaPi-Ⅱa was increased significantly in NPP-supplementation groups of 0.10-0.20% compared with that in NPP-supplementation groups of 0.25% and 0.30% (p < 0.0001). The results indicated that a reduction in NPP supplementation to 0.15% (dietary NPP level = 0.27%) with phytase inclusion did not have an adverse effect on the production performance or bone health of laying hens from 69 to 78 weeks of age, which might be attributed to renal phosphorus reabsorption and bone resorption. These findings could support the application of low-phosphorus diets in the poultry industry.

Elsholtzia bodinieri Vaniot ameliorated acute lung injury in mice by regulating pyroptosis, inflammation, oxidative stress and macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Elsholtzia bodinieri Vaniot, perennial herbs, a traditional Yunnan Chinese herbal medicine. Its whole herb can be used as commonly used herbs to cure fever, headache, inflammation, indigestion etc., and its tender tip can also be used as tea in Yunnan of China. However, the protective mechanism of Elsholtzia bodinieri Vaniot on acute lung injury (ALI) still needs to be explored. AIM OF STUDY: ALI is characterized by acute respiratory inflammation, which remains a significant source of morbidity and mortality. The current study with the aim of determining the therapeutic the efficacy of E. bodinieri Vaniot on lipopolysaccharide-induced ALI, moreover uncovered the underlying gene-regulated framework, so E. bodinieri Vaniot might serve as functional food for adjuvant therapy or therapeutic agent. MATERIALS AND METHODS: These potential pharmacological targets of E. bodinieri Vaniot against ALI were analyzed by multiple bioinformatics databases. E. bodinieri Vaniot methanol extract (EBE) was obtained by ultrasonic-assisted extraction method, and detected by UHPLC-ESI-HRMS/MS. These pyroptosis, inflammation and oxidative stress associated factors were measured using ELISA assay, western blotting, and histopathological examination to assess the effects of EBE. EcoTyper and immunofluorescence staining were employed to estimate macrophage polarization states in ALI lungs tissue. RESULTS: In ALI lung tissues, EBE treatment could increase B cell leukemia/lymphoma 2 (BCL2) to inhibit pyroptosis, downregulate prostaglandin-endoperoxide synthase 2 (PTGS2) to attenuate inflammation, upregulating NAD(P)H dehydrogenase, quinone 1 (NQO1) to alleviate oxidative stress and induce macrophage polarization toward the M2 phenotype. CONCLUSION: E. bodinieri Vaniot ameliorated ALI thought regulating pyroptosis, inflammation, oxidative stress and macrophage polarization, as well as could be a promising source for therapeutic agent.

Confusoside, a dihydrochalcone glucoside, prevents acetaminophen-induced liver injury by modulating the Nrf2/NF-κB/caspase signaling pathway.

Dihydrochalcones are important bioactive ingredients in plants. Anneslea fragrans is an edible and medicinal plant, and its leaves are rich in dihydrochalcones. Confusoside (CF) is the most abundant dihydrochalcone in A. fragrans leaves, which is traditionally used in the treatment of liver diseases. The aim of this study was to investigate the hepatoprotective effect of CF on acetaminophen (APAP)-induced hepatic injury in mice. CF could reduce the levels of AST, ALT, and LDH in the serum and enhance the antioxidant activity by activating the Nrf2 signaling pathway to increase the activities of antioxidant enzymes (SOD and CAT), and the GSH content but decrease the MDA accumulation in liver tissues. Immunofluorescence assay and western blotting analysis showed that CF can regulate Nrf2 into the cell nucleus, thereby promoting the expression of downstream antioxidant-related proteins, including NQO1 and HO-1. In addition, CF could inhibit the liver inflammatory response by suppressing the activation of the NF-κB signaling pathway to reduce the expressions of TNF-α, IL-1ß, IL-6, and NO. Molecular docking results showed that there was good binding between the CF and Keap1-Nrf2 protein. Western blotting and TUNEL analysis also revealed CF-inhibited cell apoptosis-related protein expression (Bcl2 and caspase-3/9 proteins). Thus, the CF from A. fragrans leaves could be served as an alternative hepaprotective agent for the treatment and prevention of APAP-induced liver injury.

Effect of ultra-high pressure pretreatment on the phenolic profiles, antioxidative activity and cytoprotective capacity of different phenolic fractions from Que Zui tea.

This study aims to explore whether ultra-high pressure (UHP) pre-treatment strengthened the bioaccessibility and bioactivities of the free (QF), esterified (QE) and insoluble-bound phenolics (QIB) from Que Zui tea (QT). The results revealed that the extraction yields, the total phenolic (TPC) and total flavonoid contents (TFC) of three phenolic fractions from QT were markedly increased after ultra-high pressure (UHP) processing (p < 0.05). A total of 19 and 20 compounds were characterized and quantified in non- and UHP-treated QT, respectively, including the content of 6'-O-caffeoylarbutin (11775.68 and 13248.87 µg/g of dry extract) was highest in QF, the content of caffeic acid was highest in QE (2131.58 and 7362.99 µg/g of dry extract) and QIB (9151.89 and 10930.82 µg/g of dry extract). QF, QE and QIB from QT after UHP processing had better antioxidant, ROS scavenging, and anti-apoptosis effects. The possible mechanism of cytoprotective effect was related to Keap1-Nrf2 pathway.

High throughput-screening of native herbal compounds identifies taccaoside A as a cytotoxic compound that mediates RAS signaling in cancer stem cells.

BACKGROUND: Cancer stem cells (CSCs) are characterized by their ability to self-renew, to differentiate into multiple cell types and also drive tumor formation, altogether making them important cellular targets for therapeutic intervention. However, existing CSC-targeting drugs do not significantly improve clinical outcomes. More recently, preclinical studies of natural product-derived compounds have demonstrated their potential usefulness as a therapeutic cancer treatment through their cytotoxic actions on CSCs. PURPOSE: Here, we identify CSC-specific compounds derived from natural products and characterize their putative mechanisms of action in CSCs. METHODS: Glioblastoma stem cells (GSCs) were labeled with EGFP via homologous recombination and utilized for a high-throughput screen of 8,344 fractions from 386 herbal medicines. The fractions that extinguished EGFP fluorescence signal were then further characterized by LC-MS/MS. Next, several putative cytotoxic compounds were evaluated for their cytotoxic effects on GSCs, cancer cell lines and immortalized cells using a variety of methods to study cell proliferation (EdU incorporation assay), cell death (cleaved-Caspase-3 immunostaining), DNA damage (comet assay), mitochondrial membrane changes (JC-1 immunostaining), and tumor formation in vitro (soft agar colony forming assay). We also performed surface plasmon resonance analysis, western blotting, and immunohistochemistry to characterize the putative mechanisms underlying the cytotoxic effects of putative compounds on GSCs. Finally, we carried out xenograft tumor growth assays to study the cytotoxic potential of several candidates in vivo. RESULTS: Our high throughput screen led to the identification of the furostanol saponin taccaoside A and its two homologs from the rhizomatous geophyte Tacca. subflabellata that were cytotoxic to GSCs. Interestingly, the cytotoxic effect of taccaoside A on cell lines was significantly less compared to its homologs, owing to stereochemical differences of a carbon-carbon double bond between C-20 and C-22. Molecular studies revealed that taccaoside A binds to RAS to inhibit downstream effector signaling. Correspondingly, blockade of the interaction between taccaoside A and RAS abolished the inhibitory effect of this compound on CSCs. Furthermore, taccaoside A treatment was effective in limiting tumor cell growth in vivo. CONCLUSION: Our study yielded an effective approach to screen for CSC-specific agents. Through this approach, we identified taccaoside A from the rhizomatous geophyte Tacca. subflabellata are cytotoxic to CSCs through a molecular mechanism that involves RAS binding and suppression of its downstream signaling. Our findings indicate taccaoside A is a potential lead compound for anti-CSC drug discovery.

Parent-Performed Infant Massage for Improving Parental Mental State Within 18 Months Postpartum: A Systematic Review.

The aim of the current review was to assess whether parent-performed infant massage (PPIM) could effectively improve the mental state of parents during the postpartum period. Several international electronic databases were thoroughly searched for relevant articles. Included studies observed the influence of PPIM on the mental state of parents of healthy full-term infants within 18 months postpartum or medically stable preterm infants during hospitalization after birth. Nine studies were included, which observed one or more aspects of parental mental state, including depression, anxiety, parental stress, or general mood state. Characteristics of participants, massage protocols, and outcome measures were heterogenous; hence, results regarding the influence of PPIM on parental mental state were inconsistent. Upon further investigation, 10-minute, home-based PPIM for at least 4 weeks is advisable for maternal depression within 5 months postpartum. Moreover, PPIM in a neonatal intensive care unit is advisable for improving the general mood of mothers of preterm infants. Additional methodologically rigorous studies are needed to provide stronger evidence. [Journal of Psychosocial Nursing and Mental Health Services, 61(4), 52-59.].

Dimeric benzylisoquinoline alkaloids from Thalictrum delavayi and their biological activities.

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A-E (1-5), together with six known congeners (6-11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A-E (1-5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC50 value of 2.1 µM, compared with the positive CPT-11 (IC50 = 3.0 µM). In addition, 5-7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents.

Effect of Vitamin D and/or Calcium Supplementation on Pancreatic ß-Cell Function in Subjects with Prediabetes: A Randomized, Controlled Trial.

So far, the potential role of vitamin D in ß-cell function remains a matter of debate. Therefore, a randomized, placebo-controlled trial (RCT) was conducted to evaluate the effect of a vitamin D supplement with or without calcium on ß-cell function in a Chinese population with prediabetes. Two hundred and forty-three subjects were randomly assigned in a 2-by-2 factorial-design RCT to receive either 1600 IU/day vitamin D3 with/or 500 mg/day calcium for 24 weeks. The results showed that oral administration of vitamin D and calcium could increase the secretion of insulin. Vitamin D-insufficient individuals displayed an increment in the disposition index (adjusted change = 0.31, 95%CI: 0.07, 0.56) after treatment by vitamin D + calcium. It illustrated that supplementation with vitamin D and calcium might improve the function of pancreatic ß-cell in prediabetes with low serum 25(OH)D levels. However, further studies are needed to confirm the findings. Given the low vitamin D content in natural foods, it is necessary to fortify processed foods with vitamin D.

Steroidal alkaloid with unprecedented triheterocyclic architecture.

Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from Veratrum stenophyllum, and its structure was established via spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities in vitro and in vivo.