Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation.

Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.

Systematic Myostatin Expression Screening Platform for Identification and Evaluation of Myogenesis-Related Phytogenic in Pigs.

Skeletal muscle growth in livestock impacts meat quantity and quality. Concerns arise because certain feed additives, like beta-agonists, may affect food safety. Skeletal muscle is a specialized tissue consisting of nondividing and multinucleated muscle fibers. Myostatin (MSTN), a protein specific to skeletal muscle, is secreted and functions as a negative regulator of muscle mass by inhibiting the proliferation and differentiation of myoblasts. To enhance livestock muscle growth, phytogenic feed additives could be an alternative as they inhibit MSTN activity. The objective of this study was to establish a systematic screening platform using MSTN activity to evaluate phytogenics, providing scientific evidence of their assessment and potency. In this study, we established a screening platform to monitor myostatin promoter activity in rat L8 myoblasts. Extract of Glycyrrhiza uralensis (GUE), an oriental herbal medicine, was identified through this screening platform, and the active fractions of GUE were identified using a process-scale liquid column chromatography system. For in vivo study, GUE as a feed additive was investigated in growth-finishing pigs. The results showed that GUE significantly increased body weight, carcass weight, and lean content in pigs. Microbiota analysis indicated that GUE did not affect the composition of gut microbiota in pigs. In summary, this established rodent myoblast screening platform was used to identify a myogenesis-related phytogenic, GUE, and further demonstrated that the active fractions and compounds inhibited MSTN expression. These findings suggest a novel application for GUE in growth performance enhancement through modulation of MSTN expression. Moreover, this well-established screening platform holds significant potential for identifying and assessing a diverse range of phytogenics that contribute to the process of myogenesis.

Acupuncture-related treatments improve cognitive and physical functions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine acupuncture-related treatments' effects and duration on improving cognitive function, physical function, and quality of life in patients with Alzheimer's disease. DATA SOURCES: Eight electronic databases were searched for eligible randomized controlled trials from database inception to January 2021, including Medline, PubMed, EBSCO, Embase, Cochrane, Airiti Library, China National Knowledge Infrastructure, and China Journal Full-text Database. REVIEW METHODS: A systematic review and meta-analysis were conducted on acupuncture types, cognitive function, activity of daily life, muscle strength and quality of life. RESULTS: Sixty-six studies in total with 4191 participants, the overall risk of bias was classified 60% as low and 24% as high. Acupuncture-related treatments for cognitive function and self-care ability revealed a moderate effect size, with a significant difference in noninvasive and invasive remedies (p < 0.001). Cognitive function showed significant differences in 6, 8, 12, and 24 weeks while self-care ability in the latter two weeks (p < 0.001). Meta-regression analysis showed cognitive function increased by 0.05 points (p = 0.002) and self-care ability decreased by 0.02 points (p = 0.04) after weekly treatment. There was a significant difference in muscle strength (p = 0.0003). CONCLUSION: Acupuncture-related treatments effectively improved cognitive function with the treatment lasted 6 weeks at least, but self-care ability started showing effects after 12 weeks of treatment. The improvement of muscle strength was also confirmed. Acupuncture-related treatments, particularly noninvasive ones, have few complications and high safety, perhaps providing patients and caregivers diversified choices and clinical care guidelines for reference.

Toxicity study of Bidens pilosa in animals.

Bidens pilosa (BP) is an edible Asteraceae plant found worldwide that has traditionally been used as food without noticeable side effects. BP has also been used as an herbal medicine to treat over 41 categories of disease in humans and animals. However, to date no long-term toxicity study of BP has been conducted in animals. In this study, 24-week oral toxicity of BP at doses of 0%, 0.5%, 2.5%, 5% and 10% of food was investigated in mice. Mortality, body weight, organ weight, food intake, water consumption, hematology, serum biochemistry, urinalysis, genotoxicity and organ histopathology of animals of both sexes were analyzed. No significant difference in the above parameters was observed between control and BP-fed mice except that body weight and food intake in those fed with 10% BP were significantly less than controls. In addition, similar results were seen in chickens fed with BP for 28 days. Collectively, the data demonstrate that BP has no adverse effects in mice and chickens at dose of 5% or less of food.

Item Selection Criteria With Practical Constraints in Cognitive Diagnostic Computerized Adaptive Testing.

For item selection in cognitive diagnostic computerized adaptive testing (CD-CAT), ideally, a single item selection index should be created to simultaneously regulate precision, exposure status, and attribute balancing. For this purpose, in this study, we first proposed an attribute-balanced item selection criterion, namely, the standardized weighted deviation global discrimination index (SWDGDI), and subsequently formulated the constrained progressive index (CP_SWDGDI) by casting the SWDGDI in a progressive algorithm. A simulation study revealed that the SWDGDI method was effective in balancing attribute coverage and the CP_SWDGDI method was able to simultaneously balance attribute coverage and item pool usage while maintaining acceptable estimation precision. This research also demonstrates the advantage of a relatively low number of attributes in CD-CAT applications.

Bidens pilosa and its active compound inhibit adipogenesis and lipid accumulation via down-modulation of the C/EBP and PPARγ pathways.

Obesity and its complications are a major global health problem. In this study, we investigated the anti-obesity effect and mechanism of an edible plant, Bidens pilosa, and its active constituent. We first assessed the long-term effect of B. pilosa on body composition, body weight, blood parameters in ICR mice. We observed that it significantly decreased fat content and increased protein content in ICR mice. Next, we verified the anti-obesity effect of B. pilosa in ob/ob mice. It effectively and dose-dependently reduced fat content, adipocyte size and/or body weight in mice. Moreover, mechanistic studies showed that B. pilosa inhibited the expression of peroxisome proliferator activated receptor γ (PPARγ), CCAAT/enhancer binding proteins (C/EBPs) and Egr2 in adipose tissue. Finally, we examined the effect of 2-ß-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHT) on adipogenesis in adipocytes. We found that B. pilosa significantly decreased the adipogenesis and lipid accumulation. This decrease was associated with the down-regulation of expression of Egr2, C/EBPs, PPARγ, adipocyte Protein 2 (aP2) and adiponectin. In summary, this work demonstrated that B. pilosa and GHT suppressed adipogenesis and lipid content in adipocytes and/or animals via the down-regulation of the Egr2, C/EBPs and PPARγ pathways, suggesting a novel application of B. pilosa and GHT against obesity.

Reliability and validity of the Chinese Version of the Mood Disorder Questionnaire.

The purpose of this study was to examine the reliability, validity, sensitivity, and specificity of the Chinese Version of the Mood Disorder Questionnaire (MDQ-C). A total of 170 patients were administered the Mini International Neuropsychological Interview and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision as criterion standard by on-site psychiatrists. The Cronbach's alpha, test-retest reliability, and the content validity index of the MDQ-C were .83, .76, and .80, respectively. Factor analysis revealed that two factors, elevated mood overactivity and irritable behavior, explained 40.89% of the variance. On the basis of the sensitivity and specificity results, the optimal cutoff point was 6. The MDQ-C is an effective short and comprehensive tool with robust psychometric properties for diagnosis of bipolar disorders, specifically for patients with bipolar I.

Psychometric properties of the Chinese version of the Bipolar Spectrum Diagnostic Scale.

AIM AND OBJECTIVES: The aim of this study was to test the psychometric properties of the Chinese version of the Bipolar Spectrum Diagnostic Scale (C-BSDS) in a Chinese population to serve as an aid to clinical diagnosis of bipolar disorders. BACKGROUND: Bipolar spectrum disorders are often misdiagnosed because of the wide range of symptoms seen in patients. The consequences of delayed diagnoses or misdiagnoses can be devastating. DESIGN: A cross-sectional research design. METHOD: Two hundred patients with affective disorders from a psychiatric outpatient clinic in Taiwan were enrolled. Internal consistency reliability and two-week test-retest reliability were performed to evaluate the reliability of the C-BSDS. Expert content validity and factor analysis were used for testing construct validity. To evaluate sensitivity and specificity, the Chinese version of the Mini International Neuropsychiatric Interview (MINI) was used as the gold standard for diagnosis. RESULTS: The internal consistency coefficient measured by intra-class correlation (ICC) was 0.81, the test-retest reliability coefficient was 0.85 and the expert validity was 0.85. For construct validity, 'irritable and hyper-energetic factors' and 'depressed and lack of energy factors' were extracted by factor analysis. These two factors reflected the structure of the original scale and accounted for 33.27% of the variance. The optimal cut-off was 12, which yielded a sensitivity of 74 and a specificity of 0.97 for detecting bipolar disorder and for bipolar II disorder these were 0.79 and 0.68, respectively. CONCLUSIONS: The C-BSDS showed good reliability and validity, and the results were consistent with the English version of the BSDS. Therefore, the C-BSDS is an effective tool for evaluation of a Chinese population. RELEVANCE TO CLINICAL PRACTICE: The BSDS can further increase the detection rate of bipolar disorders, especially bipolar II disorder, with satisfactory sensitivity and specificity. It can effectively assist with clinical screening of patients for bipolar spectrum disorders.