Pharmacological and mechanistic aspects of quercetin in osteoporosis.

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/ß-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

The relationship between adolescent risk perception and emotions during the COVID-19: a short-term longitudinal study.

This study explores the relationship between adolescents' perceptions of epidemic risk and their emotions through three follow-up surveys during the early stages of the COVID-19 pandemic on February 11th (T1), 18th (T2), and 25th (T3), 2020. Three hundred and four adolescents in different academic stages (junior high middle school, senior high middle school, and university) participated in the online survey, and cross-lag analysis was used to examine the causal relationship between epidemic risk perceptions and positive and negative emotions. The results found that the individual's positive emotions were significantly higher than the negative emotions in T1, T2 and T3. Cross-lag analysis found that for positive emotions, T2 positive emotions could negatively predict T3 epidemic risk perceptions, and T2 epidemic risk perceptions could negatively predict the individual's T3 positive emotions. For negative emotions, risk perceptions at T1 could positively predict negative emotions at T2, and at the same time, negative emotions at T1 could also positively predict epidemic risk perceptions at T2. This indicates that during the early stages of the COVID-19 pandemic, there was a causal relationship between the perceptions of epidemic risk and the emotions of adolescents, and this relationship had high stability among groups of different genders and academic stages.

Effects of Probiotic Supplementation on Inflammatory Markers and Glucose Homeostasis in Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Several studies have revealed the effect of probiotic supplementation in patients with type 2 diabetes (T2DM) on the amelioration of low-grade inflammation, which plays an important role in the pathogenesis of T2DM. However, the effects of the clinical application of probiotics on inflammation in individuals with T2DM remain inconsistent. This study aims to investigate the comprehensive effects of probiotics on inflammatory markers in adults with T2DM. Methods: PubMed, Embase, Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) exploring the effect of probiotic supplementation on inflammatory markers in individuals with T2DM through March 11, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We used a random-effects model to calculate the standardized mean difference (SMD) between the probiotic supplementation and control groups. Results: Seventeen eligible studies were selected with a total of 836 participants, including 423 participants in probiotic supplementation groups and 413 participants in control groups. Our study demonstrated that compared with the control condition, probiotic intake produced a beneficial effect in reducing the levels of plasma inflammation markers, including tumour necrosis factor-α (TNF-α) (SMD [95% CI]; -0.37 [-0.56, -0.19], p < 0.0001) and C-reactive protein (CRP) (SMD [95% CI]; -0.21 [-0.42, -0.01], p = 0.040), while it had no effect on the plasma interleukin-6 (IL-6) level (SMD [95% CI]; -0.07 [-0.27, 0.13], p = 0.520). In addition, our results support the notion that probiotic supplementation improves glycaemic control, as evidenced by a significant reduction in fasting blood glucose (FPG), HbA1c and HOMA-IR (SMD [95% CI]: -0.24 [-0.42, -0.05], p = 0.010; -0.19 [-0.37, -0.00], p = 0.040; -0.36 [-0.62, -0.10], p = 0.006, respectively). Conclusion: Our study revealed some beneficial effects of probiotic supplementation on improving inflammatory markers and glucose homeostasis in individuals with T2DM. Probiotics might be a potential adjuvant therapeutic approach for T2DM.

The Potential Role of Probiotics in Controlling Overweight/Obesity and Associated Metabolic Parameters in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of overweight/obesity in adults is raised to 39%, which is nearly tripled more than 1975. The alteration of the gut microbiome has been widely accepted as one of the main causal factors. To find an effective strategy for the prevention and treatment of overweight/obesity, a systematic review and meta-analysis were designed. METHODS: In this study, we systematically reviewed the article published from January 2008 to July 2018 and conducted a meta-analysis to examine the effects of probiotics on body weight control, lipid profile, and glycemic control in healthy adults with overweight or obesity. The primary outcomes were body weight, body mass index (BMI), waist circumference, fat mass, fat percentages, plasma lipid profiles, and glucose metabolic parameters. RESULTS: We systematically searched PubMed, Embase, and the Web of Science and identified 1248 articles, and 7 articles which were manually searched by the references of included studies and previously systematic reviews. Twelve randomized controlled trials (RCTs), including 821 participants, were included in the meta-analysis via full-text screening. Probiotics supplementation resulted in a statistical reduction in body weight (WMD [95% CI]; -0.55 [-0.91, -0.19] kg), BMI (WMD [95% CI]; -0.30 [-0.43, -0.18] kg m-2), waist circumference (WMD [95% CI]; -1.20 [-2.21, -0.19] cm), fat mass (WMD [95% CI]; -0.91 [-1.19, -0.63] kg), and fat percentage (WMD [95% CI]; -0.92 [-1.27, -0.56] %) compared with control groups. As expected, the metabolic parameters were improved significantly, with a pooled standardized mean difference in TC (SMD [95% CI]; -0.43 [-0.80, -0.07]), LDL-C (SMD [95% CI]; -0.41 [-0.77, -0.04]), FPG (SMD [95% CI]; -0.35 [-0.67, -0.02]), insulin (SMD [95% CI]; -0.44 [-0.84, -0.03]), and HOMA-IR (SMD [95% CI]; -0.51 [-0.96, -0.05]), respectively. The changes in TG (SMD [95% CI]; 0.14 [-0.23, 0.50]), HDL-C (SMD [95% CI]; -0.31 [-0.70, 0.07]), and HbA1c (SMD [95% CI]; -0.23 [-0.46, 0.01]) were not significant. CONCLUSION: This study suggests that the probiotics supplementation could potentially reduce the weight gain and improve some of the associated metabolic parameters, which may become an effective strategy for the prevention and treatment of obesity in adult individuals.

Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus.

Reconstruction of the anisotropic structure and proper function of the knee meniscus remains an important challenge to overcome, because the complexity of the zonal tissue organization in the meniscus has important roles in load bearing and shock absorption. Current tissue engineering solutions for meniscus reconstruction have failed to achieve and maintain the proper function in vivo because they have generated homogeneous tissues, leading to long-term joint degeneration. To address this challenge, we applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce spatial regulation of fibrochondrocyte differentiation, resulting in physiological anisotropy in the engineered meniscus. Using a customized dynamic tension-compression loading system in conjunction with two growth factors, we induced zonal, layer-specific expression of type I and type II collagens with similar structure and function to those present in the native meniscus tissue. Engineered meniscus demonstrated long-term chondroprotection of the knee joint in a rabbit model. This study simultaneously applied biomechanical, biochemical, and structural cues to achieve anisotropic reconstruction of the meniscus, demonstrating the utility of anisotropic engineered meniscus for long-term knee chondroprotection in vivo.

The effect of cassia seed extract on the regulation of the LKB1-AMPK-GLUT4 signaling pathway in the skeletal muscle of diabetic rats to improve the insulin sensitivity of the skeletal muscle.

BACKGROUND: This study aimed to observe the hypoglycemic effect of cassia seed extract in rats with type-2 diabetes mellitus and its effect on reducing insulin resistance in the skeletal muscle. METHODS: 50 rats were randomly divided into the normal, model, high-dose, middle-dose, and low-dose groups of cassia seed extract (n = 10 each). A high-fat diet combined with streptozotocin administration was adopted to build type 2 diabetes models. The cassia seed extract groups were fed different concentrations cassia seed extract while the normal and model groups were fed the same volume of normal saline. The weight, FINS, GIR, insulin tolerance, blood glucose and blood lipid level, oxidative stress indices and expressions related to the LKB1-AMPK-GLUT4 pathway were detected and compared between the two groups. RESULTS: Compared with the normal group, the model group showed lower weight, glucose infusion rate and expressions related to LKB1-AMPK-GLUT4 pathway and higher FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices (all P < 0.05). Compared with the model group, higher weight, glucose infusion rate and expressions related to LKB1-AMPK-GLUT4 pathway and lower FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices were observed in all groups that were administered cassia see extract (all P < 0.05). CONCLUSION: Cassia seed extract could noticeably improve the insulin resistance of diabetic rats and enhance the insulin sensitivity of their skeletal muscles. Its mechanism may be related to damage repair of the LKB1-AMPK-GLUT4 signaling pathway and oxidative stress in the skeletal muscle.