Rational Design of Reversible Redox Shuttle for Highly Efficient Light-Driven Microswimmer.

The light-driven micro/nanomotor (LMNM) is machinery that harvests photon energy and generates self-propulsion in varieties of liquid media. Though visions are made that these tiny swimming machines can serve future medicine for accurate drug delivery and noninvasive microsurgery, their biomedical application is still impeded by the insufficient propulsion efficiency. Here we provide a holistic model of LMNM by considering (i) photovoltaic, (ii) electrochemical, and (iii) electrokinetic processes therein. Such a quantitative model revealed the pivotal role of reaction kinetics and diffusion properties of shuttle ions in the propulsion efficiency of LMNM. With the guidance of this model, a group of ferrocene-based reversible redox shuttles, which generate slow-diffusion ions, was identified, showcasing a high locomotion velocity of ∼500 µm/s (∼100 body length per second) at an ultralow concentration (70 µM). Owing to the in-depth understanding of the fundamental energy conversion processes in LMNM, we anticipate that the development of other high-performance supporting chemicals and LMNM systems will be greatly motivated, foreseeing the advent of LMNM systems with superior efficiency.

Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice.

BACKGROUND: Nicotinamide mononucleotide (NMN) has been shown to stimulate oxidative phosphorylation in mitochondria and to improve various pathologies in patients and mouse disease models. However, whether NMN mediates mitochondrial energy production and its mechanism of action in depressed animals remain unclear. METHODS: Mice were subcutaneously injected with corticosterone (CORT; 20 mg/kg) each day for 6 weeks, while another group was given an additional dose of NMN (300 mg/kg) by oral gavage in the last 2 weeks. Then, transcriptome analyses, metabolome analyses and transient gene knockdown in primary mouse cells were performed. RESULTS: NMN administration alleviated depression-like behavior and the liver weight to body weight ratio in a mouse model of CORT-induced depression. Transcriptome and metabolome analyses revealed that in depressed mice, NMN reduced the mRNA expression of genes involved in fatty acid synthesis, stimulation of ß-oxidation and glycolysis, and increased production of acetyl-coenzyme A for the tricarboxylic acid cycle. Importantly, NMN supplementation increased NAD+ levels to enhance sirtuin (SIRT)3 activity, thereby improving mitochondrial energy metabolism in the hippocampus and liver of CORT-treated mice. Sirt3knockdown in primary mouse astrocytes reversed the effect of NMN by inhibiting energy production, although it did not affect NAD+ synthesis LIMITATIONS: Group sample sizes were small, and only one type of primary mouse cell was used CONCLUSION: These results provide evidence for the beneficial role of NMN in energy production and suggest that therapeutic strategies that increase the level of NMN can be an effective treatment for depression.

Crocin-I ameliorates the disruption of lipid metabolism and dysbiosis of the gut microbiota induced by chronic corticosterone in mice.

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive drugs. However, chronic treatment with GCs in clinical settings has a series of side effects, such as metabolic disorders, gut microbiota dysbiosis and neurological impairment. Therefore, searching for a functional substance that can alleviate these side effects is greatly meaningful to clinical patients. Crocin is the main active ingredient of saffron, which has been reported to have numerous pharmacological activities. However, the action of crocin-I, one major member of the crocin family, on the physiological mediation in the individuals receiving GC treatment remains unclear. In this study, we aimed to evaluate the efficacy of crocin-I on lipid metabolism and the gut microbiota in a mouse model of chronic corticosterone (CORT) treatment. Our findings showed that crocin-I reduced the levels of triglycerides and total cholesterol and the ratio of low density lipoprotein to high density lipoprotein in the serum of CORT-treated mice. In addition, transcriptome analysis revealed that crocin-I was effective in mediating the amelioration of lipid metabolism, mainly in fatty acid metabolism and steroid biosynthesis in CORT-treated mice. Moreover, metabolome analysis demonstrated that crocin-I could restore the disturbed metabolites in the liver of CORT-treated mice, most of which are long-chain fatty acids. Furthermore, high-throughput sequencing of 16s rRNA revealed that crocin-I could mitigate the dysbiosis of the gut microbiota caused by CORT at a dose of 40 mg kg-1, by resulting in a significant increase in the alpha diversity of the microbes in the cecal contents and a significant reduction in the abundance of Firmicutes, whereas by increasing the abundance of Bacteroidetes. These results indicated that oral administration of crocin-I could modify the composition of the gut microbiota and alleviate hepatic lipid disorder in mice treated with a high dose of GCs.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

The quality of reporting of randomized controlled trials of traditional Chinese medicine: a survey of 13 randomly selected journals from mainland China.

BACKGROUND: The number of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) is increasing. However, there have been few systematic assessments of the quality of reporting of these trials. OBJECTIVE: This study was undertaken to evaluate the quality of reporting of RCTs in TCM journals published in mainland China from 1999 to 2004. METHODS: Thirteen TCM journals were randomly selected by stratified sampling of the approximately 100 TCM journals published in mainland China. All issues of the selected journals published from 1999 to 2004 were hand-searched according to guidelines from the Cochrane Centre. All reviewers underwent training in the evaluation of RCTs at the Chinese Centre of Evidence-based Medicine. A comprehensive quality assessment of each RCT was completed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist (total of 30 items) and the Jadad scale. Disagreements were resolved by consensus. RESULTS: Seven thousand four hundred twenty-two RCTs were identified. The proportion of published RCTs relative to all types of published clinical trials increased significantly over the period studied, from 18.6% in 1999 to 35.9% in 2004 (P < 0.001). The mean (SD) Jadad score was 1.03 (0.61) overall. One RCT had a Jadad score of 5 points; 14 had a score of 4 points; and 102 had a score of 3 points. The mean (SD) Jadad score was 0.85 (0.53) in 1999 (746 RCTs) and 1.20 (0.62) in 2004 (1634 RCTs). Across all trials, 39.4% of the items on the modified CONSORT checklist were reported, which was equivalent to 11.82 (5.78) of the 30 items. Some important methodologic components of RCTs were incompletely reported, such as sample-size calculation (reported in 1.1% of RCTs), randomization sequence (7.9%), allocation concealment (0.3 %), implementation of the random-allocation sequence (0%), and analysis of intention to treat (0%). CONCLUSION: The findings of this study indicate that the quality of reporting of RCTs of TCM has improved, but remains poor.

Compound salvia pellet, a traditional Chinese medicine, for the treatment of chronic stable angina pectoris compared with nitrates: a meta-analysis.

BACKGROUND: Compound salvia pellet (CSP), consisting of active herbal ingredients extracted from Danshen (salvia miltiorrhiza), Sanqi (panax notoginseng), and Borneol (Cinnamomum camphora), is taken most frequently by patients with angina pectoris in China. To determine the efficacy and safety of CSP for the treatment of stable angina pectoris (SAP), a meta-analysis was undertaken. MATERIAL/METHODS: An extensive search including MEDLINE, EMBASE, BA, Chinese Biomedical Database (CBM), and Chinese Cochrane Centre Controlled Trials Register from 1994 to 2004 was performed. Data were extracted independently from the included trials by two reviewers. Statistical software (RevMan 4.1) provided by the Cochrane Collaboration was applied. RESULTS: Twenty-seven randomized controlled trials (RCTs) (n=3722), regardless of language or publication status, were identified. Generally, the methodological quality of the trials, assessed by the Jadad scale, was low, except for one with 3 points. Statistical pooling of the results showed that, compared with nitrates, CSP treatment had significant effect on the improvement of angina symptoms (RR=1.13, 95%CI=[1.07, 1.20]), showed greater increased effect on the improvement of electrocardiogram (ECG) results (RR=1.39, 95%CI=[1.28, 1.50]), and the percentage of patients with adverse events was significantly decreased in the treatment of CSP in comparison with nitrates (2.4% vs. 29.7%). CONCLUSIONS: CSP has significant effect on the improvement of angina symptoms and ECG results with few adverse events. However, the methodological quality of clinical trials with CSP for SAP needs to be improved, and the outcome measures should include mortality, quality of life, and other end-points.

Relationship between bone mineral density and syndrome types described in traditional chinese medicine in chronic obstructive pulmonary disease: a preliminary clinical observation.

Osteoporosis is a common finding following chronic obstructive pulmonary disease (COPD), but there are few reports on the relationship between bone mineral density (BMD) and the syndrome types described in traditional Chinese medicine (TCM) in patients with COPD. A cross-sectional medical survey was used in this study. Twenty-six male patients with COPD and 26 age-matched male healthy subjects were recruited. The symptom questionnaire survey of TCM was implemented, and thereafter the COPD patients were divided into two subgroups: type of deficiency of the lung and spleen (TDLS) and type of deficiency of the lung, spleen and kidney (TDLSK). BMD of lumbar spine (L2-4), non-dominant femoral neck (Neck), Ward's triangle (Ward's), and great trochanter (Troch) were measured by dual-energy x-ray absorptiometry. In addition, the other bone turnover markers were also examined. The results showed that BMD was much more decreased in TDLSK than that in TDLS patients (p < 0.05), and BMD in the patients of the TDLS subgroup without symptoms of kidney-vacuity has showed the decreased trend from healthy subjects to TDLS patients. Furthermore, there was a higher incidence of osteoporosis in patients with TDLSK compared with that in TDLS (p < 0.05, OR > 2.0). Therefore, the data suggest that: (1) BMD might be a marker more sensitive than the symptom for the diagnosis of kidney-vacuity in COPD patients; (2) the deficiency of kidney would be the key factor of bone mineral loss; and (3) that invigorating the kidney should be performed in the phase of TDLS in COPD patients in advance.

[Systematic assessment on randomized controlled trials for treatment of stable angina pectoris by compound salvia pellet].

OBJECTIVE: To assess the therapeutic effect and safety of compound salvia pellet (CSP) in treating stable angina pectoris (SAP). METHODS: Literatures regarding randomized clinical trials of CSP versus nitrate ester preparation in treating SAP, without any language limitation, were reviewed. Jadad scale was used to assess the methodological quality of the inclusive trials, and Cochrane systematic evaluation was applied for it. RESULTS: Seventeen randomized trials conformed to the inclusion criteria were reviewed, all in Chinese language. The combined results of the two comparing groups on therapeutic effect in symptom of angina and electrocardiogram (ECG) showed that the relative risk (RR) was 1.12 (1.06, 1.19) and the 95% credibility interval (CI) was 1.42 (1.20, 1.57). CONCLUSION: Based on the Cochrane systematic review, CSP showed the therapeutic effect in treating SAP on relieving angina and improving ECG better than that of nitrate ester preparation, and with less adverse reaction and good tolerance. However the conclusion cannot be reached yet due to the low methodological quality of the trials collecting and lacking in some important final markers and relevant criteria for quality of life, more rationally designed and strictly executed randomized trials with large samples are necessary.