Biosynthesis of CuTe Nanorods with Large Molar Extinction Coefficients for NIR-II Photoacoustic Imaging.

Photoacoustic imaging (PAI) in the second near-infrared region (NIR-II), due to deeper tissue penetration and a lower background interference, has attracted widespread concern. However, the development of NIR-II nanoprobes with a large molar extinction coefficient and a high photothermal conversion efficiency (PCE) for PAI and photothermal therapy (PTT) is still a big challenge. In this work, the NIR-II CuTe nanorods (NRs) with large molar extinction coefficients ((1.31 ± 0.01) × 108 cm-1·M-1 at 808 nm, (7.00 ± 0.38) × 107 cm-1·M-1 at 1064 nm) and high PCEs (70% at 808 nm, 48% at 1064 nm) were synthesized by living Staphylococcus aureus (S. aureus) cells as biosynthesis factories. Due to the strong light-absorbing and high photothermal conversion ability, the in vitro PA signals of CuTe NRs were about 6 times that of indocyanine green (ICG) in both NIR-I and NIR-II. In addition, CuTe NRs could effectively inhibit tumor growth through PTT. This work provides a new strategy for developing NIR-II probes with large molar extinction coefficients and high PCEs for NIR-II PAI and PTT.

Effects of Therapeutic Horseback-Riding Program on Social and Communication Skills in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Animal-assisted therapy has become a fast-growing and effective approach for remediating core impairments of children with ASD; however, recent systematic review studies on the effects of AAT in children with ASD have some limitations, including referral to a variety of animal-assisted interventions rather than to horseback-riding therapy alone and the absence of any meta-analysis in systematic reviews. A complete systematic review of the studies that describe the use of THR as an intervention is needed to specifically target the core impairments of children with ASD. The purpose of this study was to employ the systematic review method to synthesize research findings regarding the effects of THR programs on the social interaction and communication skills of children with ASD. We conducted a structured search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for potentially relevant studies in five databases (Web of Science, PubMed, CINAHL, Scopus, and SPORTDiscus) from inception until February 2022. In addition, we manually searched the bibliographies of the included studies to find articles that might otherwise have been missed. We considered articles eligible or ineligible if they satisfied specific inclusion or exclusion criteria. Our results showed that the THR program is an effective direct and alternative therapeutic program that can considerably improve the social behaviors and communication skills of children with ASD and can effectively impact autistic impairments in areas such as social awareness, social cognition, social motivation, and social communication. These findings are in line with those of previous studies; however, we did not find statistical evidence of any effect of THR on the autistic behaviors of irritability, stereotypy, and inappropriate speech. In conclusion, the findings produced by this meta-analysis study provide evidence that THR programs can considerably improve the social behaviors and communication skills of children with ASD.

Effects of a Therapeutic Horseback Riding Program on Social Interaction and Communication in Children with Autism.

Various therapeutic interventions have been studied and found to be effective in reducing the stereotypical behaviors of children with autism spectrum disorder (ASD). There has been increasing interest in using animal-assisted interventions (AAIs) as an alternative approach to therapeutic rehabilitation for children with ASD, and many studies have reported that AAI has significant benefits for the cognitive, psychological, and social behavior of children with ASD. The present study was designed to examine the effects of a 16 weeks therapeutic horseback riding program on social interaction and communication skills in children with autism. Eighty-four children diagnosed with ASD, aged between 6 and 12 years old, were recruited for this study. All selected participants met the DSM-V criteria, and a total of sixty-one participants (N = 61) completed the study. A quasi-experimental design with an experimental group and control group was implemented for this study, taking measurements at pre-test, interim-test, and post-test to monitor the behavior changes in social and communication throughout the 16-week intervention. Repeated measures ANOVA and the independent sample t-test were used for data analysis, to assess the difference between the experimental group and control group. The results indicated that the THR program had positive influences on overall social skills and communication, based on the SSIS and the ABLLS-R scores, compared to the control group (p < 0.05). A notable improvement in the overall social interaction score was observed from the interim-testing point to post-test. In addition, participants in the therapeutic horseback riding (THR) group achieved significant improvements on six out of seven items in their communication evaluations. In conclusion, after 16 weeks of intervention, the THR program significantly enhanced the subdomains of social and communication skills in the areas of social interaction, communication, responsibility, and self-control, compared to the control group.

Components characterisation of Berchemia lineata (L.) DC. by UPLC-QTOF-MS/MS and its metabolism with human liver microsomes.

Investigations were performed on the determination of the main components in Berchemia lineata (L.) DC. (BL) and its metabolism with human liver microsomes (HLM). A total of 35 compounds were detected in BL extracts and 25 of them including 6 naphthopyrones, 10 flavonoids, 2 phenolic acids, 2 phenols, 4 fatty acids and 1 quinone were unambiguously or tentatively identified by UPLC-QTOF-MS/MS. Among them, naphthopyrones were first identified in BL extracts and labelled in chromatography. In addition, the weak inhibitory effects of BL extracts (IC50＝149.25 µg/mL) and rubrofusarin-6-O-α-L-rhamnosyl-(1-6)-O-ß-D-glu-copyranside (the main component of BL extracts, M0; IC50＝82.14 µM) on CYP3A4 were also proved using testosterone as specific probe drug. The main metabolic pathway of M0 by HLM was hydroxylation in its aglycone, the metabolite was tentatively identified as 10-hydroxy-rubrofusarin-6-O-α-L-rhamnosyl-(1-6)-O-ß-D-glucopyranside. Components characterisation and the metabolism with HLM could help the further development and application of BL.

The effect of Qigong-based therapy on patients with Parkinson's disease: a systematic review and meta-analysis.

OBJECTIVE: This study was to evaluate the effects of Qigong on clinical motor symptoms, walking ability, and balance of patients with Parkinson's disease. DATA SOURCES: Seven electronic databases (MEDLINE, Web of Science, CINAHL, SportDiscus, Scopus, China National Knowledge Infrastructure, and Wanfang Database) were searched from inception to June 28, 2020. METHODS: Two reviewers independently selected and extracted the data from studies with randomized controlled trial, and effect sizes were calculated by employing random-effect models with 95% confidential interval (CI). We used Physiotherapy Evidence Database scale to evaluate the quality of included studies. RESULTS: A total of seven studies with 325 participants (180 males and 145 females) were included in this meta-analysis. Results of this meta-analysis showed that Qigong had significantly positive effects on motor symptoms (SMD = 0.59, 95% CI [0.24, 0.93]), walking ability (SMD = 0.78, 95% CI [0.10, 1.47]), and balance (SMD = 0.72, 95% CI [0.23, 1.20]) in patients with Parkinson's disease. Subgroup analysis showed Qigong exercise had significant difference on improving motor symptoms and walking ability compared to passive control (P < 0.01), and no significant difference compared to active control. Subgroup analysis of Qigong exercise revealed a significant difference on balance compared to both active and passive control (P < 0.05). In addition, meta-regression result indicated that the effect of Qigong exercise on motor symptoms was influenced by age. CONCLUSION: The findings from current meta-analysis supported Qigong exercise as a beneficial alternative therapy may contribute to increasing motor function, walking ability, and balance for patients with Parkinson's disease.

Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade.

OBJECTIVES: Wnt16 is implicated in bone fracture and bone mass accrual both in animals and humans. However, its functional roles and molecular mechanism in chondrocyte differentiation and osteoarthritis (OA) pathophysiology remain largely undefined. In this study, we analysed its mechanistic association and functional relationship in OA progression in chondrocyte lineage. METHODS: The role of Wnt16 during skeletal development was examined by Col2a1-Wnt16 transgenic mice and Wnt16fl/fl;Col2a1-Cre (Wnt16-cKO) mice. OA progression was assessed by micro-CT analysis and Osteoarthritis Research Society International score after anterior cruciate ligament transection (ACLT) surgery with Wnt16 manipulation by adenovirus intra-articular injection. The molecular mechanism was investigated in vitro using 3D chondrocyte pellet culture and biochemical analyses. Histological analysis was performed in mouse joints and human cartilage specimens. RESULTS: Wnt16 overexpression in chondrocytes in mice significantly inhibited chondrocyte hypertrophy during skeletal development. Wnt16 deficiency exaggerated OA progression, whereas intra-articular injection of Ad-Wnt16 markedly attenuated ACLT-induced OA. Cellular and molecular analyses showed that, instead of ß-catenin and calcium pathways, Wnt16 activated the planar cell polarity (PCP) and JNK pathway by interacting mainly with AP2b1, and to a lesser extend Ror2 and CD146, and subsequently induced PTHrP expression through phosphor-Raptor mTORC1 pathway. CONCLUSIONS: Our findings indicate that Wnt16 activates PCP/JNK and crosstalks with mTORC1-PTHrP pathway to inhibit chondrocyte hypertrophy. Our preclinical study suggests that Wnt16 may be a potential therapeutic target for OA treatment.

Jingshu Keli attenuates cervical spinal nerve ligation-induced allodynia in rats through inhibition of spinal microglia and Stat3 activation.

BACKGROUND CONTEXT: Cervical radicular pain resulting from mechanical compression of a spinal nerve secondary to spinal degenerative alternations negatively impacts patients' quality of life. Jingshu Keli (JSKL), a traditional Chinese medicine formula with multiple active compounds, has been prescribed for pain management in patients with cervical radiculopathy for decades. Two major components of JSKL, ferulic acid and cinnamaldehyde, were identified to have anti-inflammation effect via inhibiting activation of Stat3. PURPOSE: To investigate the efficacy of JSKL by investigating its mechanism in attenuating cervical radiculopathy-induced mechanical allodynia via modulation activation of spinal microglia and phosphorylation of signal transducer and activator of transcription 3 (Stat3). STUDY DESIGN: An in vivo animal experiment. METHODS: Cervical radiculopathy of rats was established by C7 spinal nerve ligation (SNL) with 6-0 silk suture. The effect of postoperational daily gavage of JSKL on mechanical allodynia of rats was tested on day 3, 7, and 14 after surgery. Furthermore, spinal glial cells activation and phosphorylation of Stat3 (p-Stat3) were tested with immunofluorescence imaging and Western blot. RESULT: The JSKL significantly inhibited SNL-induced allodynia as well as microglia activation in the spinal cord on day 7 and 14 after surgery. Moreover, expression of p-Stat3 was decreased in rats with SNL and JSKL treatment in comparison with rats with SNL and vehicle treatment. CONCLUSIONS: The JSKL attenuated SNL-induced mechanical allodynia in rats. This analgesic effect might be explained by the suppression of activations of spinal microglia as well as p-Stat3. Our study provides experimental evidence for JSKL as an alternative approach to manage refractory pain in patients with cervical radiculopathy.

Segmental composite porous scaffolds with either osteogenesis or anti-bone resorption properties tested in a rabbit ulna defect model.

A functional biomaterial with a therapeutic effect is desirable as an adjuvant therapy to enhance bone formation and prevent local recurrence of bone tumours, especially when the resection margins are not identifiable. In this study, novel composite materials were developed with dual properties of osteopromotion and bone resorption to mimic the tumour inhibition effect, including water-soluble phosphorylated chitosan (P-chitosan) for increasing osteoblasts activity and disodium (1 → 4)-2-deoxy-2-sulphoamino-ß-d-glucopyranuronan (S-chitosan) for inhibiting bone resorption activity. First, P-chitosan and S-chitosan were respectively incorporated into two kinds of PLGA/TCP-based scaffold, i.e. PLGA-TCP-P-chitosan (P/T/P-chitosan) and PLGA-TCP-S-chitosan (P/T/S-chitosan) scaffolds. We subsequently tested combined scaffolds of PLGA-TCP-P-S-P-chitosan (P/T/PSP-chitosan) made of P/T/P-chitosan and P/T/S-chitosan to assess their integral effect, on enhancement of bone formation with P/T/P-chitosan and inhibition of tissue regeneration with P/T/S-chitosan, in an established rabbit ulnar bone defect model to imitate bone resection post-bone tumour. To compare bone healing in the defects, the P/T/P-chitosan group was regarded as a bone formation enhancement group, while the P/T group served as a control. Bone mineral density (BMD) in the P/T/P-chitosan and P/T/PSP-chitosan groups were found to be significantly higher than those in the P/T group, while that in the P/T/P-chitosan group was greater than that in the P/T/PSP-chitosan group (p < 0.05). These findings demonstrated that P/T/PSP-chitosan scaffolds possessed more osteogenic potential than the P/T scaffold but less osteogenic effect than the P/T/P-chitosan scaffold, as the S-chitosan component inhibited the activities of osteoblasts for bone formation. These findings implied a dual function of the designed P/T/PSP-chitosan for further preclinical validation and potential applications in the prevention of local recurrence and for enhancing bone repair after bone tumour resection. Copyright © 2013 John Wiley & Sons, Ltd.

Traditional Chinese Mind and Body Exercises for Promoting Balance Ability of Old Adults: A Systematic Review and Meta-Analysis.

The purpose of this study was to provide a quantitative evaluation of the effectiveness of traditional Chinese mind and body exercises in promoting balance ability for old adults. The eligible studies were extensively searched from electronic databases (Medline, CINAHL, SportDicus, and Web of Science) until 10 May 2016. Reference lists of relevant publications were screened for future hits. The trials used randomized controlled approaches to compare the effects of traditional Chinese mind and body exercise (TCMBE) on balance ability of old adults that were included. The synthesized results of Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and static balance with 95% confidence intervals were counted under a random-effects model. Ten studies were selected based on the inclusion criteria, and a total of 1,798 participants were involved in this review. The results of the meta-analysis showed that TCMBE had no significant improvement on BBS and TUG, but the BBS and TUG could be obviously improved by prolonging the intervention time. In addition, the results showed that TCMBE could significantly improve the static balance compared to control group. In conclusion, old adults who practiced TCMBE with the time not less than 150 minutes per week for more than 15 weeks could promote the balance ability.

Effects of Health Qigong Exercises on Relieving Symptoms of Parkinson's Disease.

The purpose of this study was to investigate the effects of Health Qigong on the treatment and releasing symptoms of Parkinson's disease (PD). Fifty-four moderate PD patients (N = 54) were randomly divided into experimental and control groups. Twenty-eight PD patients were placed in the experimental group in which the prescribed medication plus Health Qigong exercise will be used as intervention. The other 26 PD patients as the control group were treated only with regular medication. Ten-week intervention had been conducted for the study, and participants completed the scheduled exercises 5 times per week for 60 minutes each time (10 minutes for warm-up, 40 minutes for the exercise, and 10 minutes for cooldown). Data which included the muscle hardness, one-legged blind balance, physical coordination, and stability was collected before, during, and after the intervention. Comparisons were made between the experimental and control groups through the Repeated Measures ANOVA. The results showed that PD patients demonstrate a significant improvement in muscle hardness, the timed "up and go," balance, and hand-eye coordination (the turn-over-jars test). There were no significant differences between the two groups in gender, age, and course of differences (P < 0.05). The study concluded that Health Qigong exercises could reduce the symptoms of Parkinson's disease and improve the body functions of PD patients in both the mild and moderate stages. It can be added as an effective treatment of rehabilitation therapy for PD.

Effects of wheelchair Tai Chi on physical and mental health among elderly with disability.

A 12-week Wheelchair Tai Chi 10 Form (WTC10) intervention was conducted among elderly with disability to examine the effect of this WTC10 intervention on selected physical and mental health variables. Thirteen (age 87.23 ± 6.71) in the WTC10 intervention group and 15 (age 89.73 ± 6.31) in the control group completed the study. Independent t-tests and paired t-tests were employed to examine the differences between groups and within groups, respectively, at pretest and post-test. The WTC10 intervention group showed significant improvements in systolic and diastolic blood pressure, shoulder external rotation, left trunk rotation and total trunk rotation after the intervention. A 12-week WTC10 intervention had positive effects on blood pressure, range of motion at the shoulder and trunk, physical activity, and mental health among the elderly with disability. WTC10 is a feasible and safe exercise for the elderly with disability.

Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) may increase the future health risks of women and their offspring. The aim of this study was to determine the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with GDM. METHODS: Forty-four pregnant women with GDM at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. RESULTS: Forty-two women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022). CONCLUSIONS: Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with GDM, and it decreased the incidence of LGA newborns.

Comparative study of two types of herbal capsules with different Epimedium species for the prevention of ovariectomised-induced osteoporosis in rats.

BACKGROUND/OBJECTIVE: Epimedii Folium is the most important osteogenic herb formulated for the traditional Chinese Medicine Xian Ling Gu Bao (XLGB) capsule. The present study compared XLGB capsules containing two different Epimedium species, i.e., either Epimedium pubescens (XEP) or Epimedium koreanum (XEK), with the focus being on the chemical constituents and antiosteoporotic efficacy. METHODS: Ultra performance liquid chromatography was used to demonstrate the different chemical constituents. Biomechanical tests, histological, and cytological evaluation were performed to characterise and compare the bone mineral density, bone strength, microstructure of bone tissue, and biological activity between XEP and XEK using an established ovariectomised (OVX) rat model. RESULTS: Six flavonoids with different contents between XEK and XEP were identified. As compared with the OVX group, significantly higher bone mineral density, elastic-modulus, and compressive strength were found in both the XEK group and XEP group (p < 0.05 for all, n = 8). Histomorphometric data presented significantly higher osteoblast surface ratio and osteoid area accompanied by significantly lower values of erosion surface and adiopocytes area in two treatment groups (p < 0.05, n = 6). XLGB Fufang with either XEK or XEP all showed significant preventive effects in OVX-induced osteoporosis and deterioration of bone mechanical properties. CONCLUSION: The significance of the current preclinical experimental study was that these two Epimedium species used for formulating XLGB capsules were equally effective for the prevention of oestrogen-depletion induced osteoporosis.

Fish Oil Supplements Lower Serum Lipids and Glucose in Correlation with a Reduction in Plasma Fibroblast Growth Factor 21 and Prostaglandin E2 in Nonalcoholic Fatty Liver Disease Associated with Hyperlipidemia: A Randomized Clinical Trial.

UNLABELLED: Fish oil has been used effectively in the treatment of cardiovascular disease via triglyceride reduction and inflammation modulation. This study aimed to assess the effects of fish oil on patients with nonalcoholic fatty liver disease (NAFLD) associated with hyperlipidemia. Eighty participants with NAFLD associated with hyperlipidemia were randomly assigned to consume fish oil (n=40, 4 g/d) or corn oil capsules (n=40, 4 g/d) for 3 months in a double-blind, randomized clinical trial. Blood levels of lipids, glucose and insulin, liver enzymes, kidney parameters and cytokines at baseline and the end of the study were measured. Seventy people finished the trial. Plasma concentrations of eicosapentaenoic acid and docosahexaenoic acid significantly increased in the fish oil group after intervention. After adjustment for age, gender and BMI, fish oil significantly decreased fasting serum concentrations of total cholesterol, triglyceride, apolipoprotein B and glucose (by (mean±SD) 0.49±0.43 mmol/L, 0.58±0.89 mmol/L, 0.28±0.33 g/L and 0.76±0.56 mmol/L, respectively, P<0.05), as well as alanine aminotransferase and γ-glutamyl transpeptidase levels (by (median (interquartile)) 9.0(0.5, 21.5) and 7.0(2.2, 20.0) IU/L, respectively, P<0.05), significantly increased serum adiponectin levels (by 1.29±0.62 µg/mL, P<0.001), and reduced serum levels of tumor necrosis factor α, leukotrienes B4, fibroblast growth factor 21 (FGF21), cytokeratin 18 fragment M30 and prostaglandin E2 (by 1.70±1.18 pg/mL, 0.59±0.28 ng/mL, 121±31 pg/mL, 83±60 IU/L and 10.9±2.3 pg/mL, respectively, P<0.001). Corn oil had no effect except for increasing serum creatinine concentrations by 7.7±8.9 µmol/L (P=0.008). The effects of fish oil on lipids, glucose and γ-glutamyl transpeptidase were positively correlated with the reductions of serum FGF21 and prostaglandin E2 concentrations after adjustment for age, gender and BMI (r = 0.275 to 0.360 and 0.261 to 0.375, respectively, P<0.05). In conclusion, our findings suggest that fish oil can benefit metabolic abnormalities associated with NAFLD treatment. TRIAL REGISTRATION: ChiCTR-TRC-12002380.

Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: A randomized controlled trial.

Ampelopsis grossedentata, a medicinal and edible plant, has been widely used in China for hundreds of years, and dihydromyricetin is the main active ingredient responsible for its various biological actions. We investigated the effects of dihydromyricetin on glucose and lipid metabolism, inflammatory mediators and several biomarkers in nonalcoholic fatty liver disease. In a double-blind clinical trial, sixty adult nonalcoholic fatty liver disease patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg) twice daily for three months. The serum levels of alanine, aspartate aminotransferase, γ-glutamyl transpeptidase, glucose, low-density lipoprotein-cholesterol and apolipoprotein B, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly decreased in the dihydromyricetin group compared with the placebo group. In the dihydromyricetin group, the serum levels of tumor necrosis factor-alpha, cytokeratin-18 fragment and fibroblast growth factor 21 were decreased, whereas the levels of serum adiponectin were increased at the end of the study. We conclude that dihydromyricetin supplementation improves glucose and lipid metabolism as well as various biochemical parameters in patients with nonalcoholic fatty liver disease, and the therapeutic effects of dihydromyricetin are likely attributable to improved insulin resistance and decreases in the serum levels of tumor necrosis factor-alpha, cytokeratin-18, and fibroblast growth factor 21.

Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.

SCOPE: Resveratrol (RSV), a natural polyphenol, has been reported to attenuate nonalcoholic fatty liver disease (NAFLD); however, its underlying mechanism is unclear. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, we investigated the role of autophagy in the beneficial effects of RSV on hepatic steatosis. METHODS AND RESULTS: Via Oil red O staining, triglyceride, and ß-hydroxybutyrate detection, we found that RSV decreased palmitate-induced lipid accumulation and stimulated fatty acid ß-oxidation in hepatocytes. Based on Western blot assay, confocal microscopy and transmission electron microscopy, we found that RSV induced autophagy in hepatocytes, whereas autophagy inhibition markedly abolished RSV-mediated hepatic steatosis improvement. Moreover, RSV increased cAMP levels and the levels of SIRT1 (sirtuin 1), pPRKA (phosphorylated protein kinase A), and pAMPK (phosphorylated AMP-activated protein kinase), as well as SIRT1 activity in HepG2 cells. Incubation with inhibitors of AC (adenylyl cyclase), PRKA, AMPK, SIRT1, or with AC, PRKA, AMPK, or SIRT1 siRNA abolished RSV-mediated autophagy. Similar results were obtained in mice with hepatic steatosis. CONCLUSION: RSV improved hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1 signaling pathway, which provides new evidence regarding RSV's effects on NAFLD treatment.

Carbohydrate electrolyte solutions enhance endurance capacity in active females.

The purpose of the present study was to investigate the effects of supplementation with a carbohydrate-electrolyte solution (CES) in active females during a prolonged session of submaximal running to exhaustion. Eight healthy active females volunteered to perform a session of open-ended running to exhaustion at 70% of their maximal oxygen consumption on a treadmill during the follicular phase of their menstrual cycle on two occasions. During each run, the subjects consumed either 3mL·kg(-1) body mass of a 6% CES or a placebo drink (PL) every 20 min during exercise. The trials were administered in a randomized double-blind, cross-over design. During the run, the subjects ingested similar volumes of fluid in two trials (CES: 644 ± 75 mL vs. PL: 593 ± 66 mL, p > 0.05). The time to exhaustion was 16% longer during the CES trial (106.2 ± 9.4 min) than during the PL trial (91.6 ± 5.9 min) (p < 0.05). At 45 min during exercise, the plasma glucose concentration in the CES trial was higher than that in PL trial. No differences were observed in the plasma lactate level, respiratory exchange ratio, heart rate, perceived rate of exertion, sensation of thirst, or abdominal discomfort between the two trials (p > 0.05). The results of the present study confirm that CES supplementation improves the moderate intensity endurance capacity of active females during the follicular phases of the menstrual cycle. However, the exogenous oxidation of carbohydrate does not seem to explain the improved capacity after CES supplementation.

Exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair.

This study was designed to develop a bioactive scaffold to enhance bone defect repair in steroid-associated osteonecrosis (SAON). Icaritin, a metabolite of the herb Epimedium, has been identified as an angiogenic and osteogenic phytomolecule. Icaritin was homogenized into poly lactic-co-glycolic acid/tricalcium phosphate (PLGA/TCP) to form an icaritin-releasing porous composite scaffold (PLGA/TCP/icaritin) by fine-spinning technology. In vitro, high performance liquid chromatography was used to determine the release of icaritin during degradation of PLGA/TCP/icaritin. The osteogenic effects of PLGA/TCP/icaritin were evaluated using rat bone marrow mesenchymal stem cells (BMSCs). In vivo, the osteogenic effect of PLGA/TCP/icaritin was determined within a bone tunnel after core decompression in SAON rabbits and angiography within scaffolds was examined in rabbit muscle pouch model. In vitro study confirmed the sustainable release of icaritin from PLGA/TCP/icaritin with the bioactive scaffold promoting the proliferation and osteoblastic differentiation of rat BMSCs. In vivo study showed that PLGA/TCP/icaritin significantly promoted new bone formation within the bone defect after core decompression in SAON rabbits and enhanced neovascularization in the rabbit muscle pouch experiment. In conclusion, PLGA/TCP/icaritin is an innovative local delivery system that demonstrates sustainable release of osteogenic phytomolecule icaritin enhancing bone repair in an SAON rabbit model. The supplement of scaffold materials with bioactive phytomolecule(s) might improve treatment efficiency in challenging orthopedic conditions.

A natural compound induced cardiogenic differentiation of endogenous MSCs for repair of infarcted heart.

An intra-myocardial injection of a cardiogenic factor (cardiogenin) was reported to induce myocardial regeneration of exogenous mesenchymal stem cell (MSCs) origin. In this study, replacement of the dangerous intra-myocardial injection with a safe method and whether the endogenous MSCs contribute to the cardiogenin-mediated myocardial regeneration were investigated. Bone marrow transplantation with labeled MSCs was performed in rats, which were subsequently subject to a permanent ligation of left anterior descending coronary artery one week after the transplantation. The rats were then treated with the cardiogenin through oral administration for 2 weeks. We not only demonstrated the substantial therapeutic effects of cardiogenin on myocardial infarction through an oral administration, but also provided direct evidences that the bone marrow derived endogenous MSCs are the major cellular source of the regenerating myocardium. Preliminary mechanistic studies suggested that miR-9 and its target E-cadherin may be required for intercalated disc formation.

A plant-derived remedy for repair of infarcted heart.

BACKGROUND: Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration. METHODS AND FINDINGS: The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium. CONCLUSIONS: This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.