A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis.

Activating Nrf2 by small molecules is a promising strategy to treat postmenopausal osteoporosis. However, there is currently no Nrf2 activator approved for treating chronic diseases, and the downstream mechanism underlying the regulation of Nrf2 on osteoclast differentiation remains unclear. Here, we found that bitopertin, a clinical-stage glycine uptake inhibitor, suppresses osteoclast differentiation and ameliorates ovariectomy-induced bone loss by activating Nrf2. Mechanistically, bitopertin interacts with the Keap1 Kelch domain and decreases Keap1-Nrf2 binding, leading to reduced Nrf2 ubiquitination and degradation. Bitopertin is associated with less adverse events than clinically approved Nrf2 activators in both mice and human subjects. Furthermore, Nrf2 transcriptionally activates ferroportin-coding gene Slc40a1 to reduce intracellular iron levels in osteoclasts. Loss of Nrf2 or iron supplementation upregulates ornithine-metabolizing enzyme Odc1, which decreases ornithine levels and thereby promotes osteoclast differentiation. Collectively, our findings identify a novel clinical-stage Nrf2 activator and propose a novel Nrf2-iron-ornithine metabolic axis in osteoclasts.

Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review.

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be accomplished effectively using protective agents. This review provides an overview of multiple studies on a wide range of protective agents and their molecular mechanisms against DON organ toxicity. Protective agents include plant extracts, yeast products, bacteria, peptides, enzymes, H2, oligosaccharides, amino acids, adsorbents, vitamins and selenium. Among these, biological detoxification of DON using microorganisms to reduce the toxicity of DON without affecting the growth performance of pigs may be the most promising detoxification strategy. This paper also evaluates future developments related to DON detoxification and discusses the detoxification role and application potential of protective agents. This paper provides new perspectives for future research and development of safe and effective feed additives.

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. METHODS: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. RESULTS: Six randomized controlled trials comprising 516 participants were included. The meta-analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (-0.66 mmol/L; 95 % CI (confidence intervals) [- 1.28, - 0.04]), plasma glucose 2 h after meal (2-h PG) (-1.18 mmol/L; 95 % CI [-1.94, -0.42]) in six RCTs, body mass index (BMI) (-3.07 mmol/L; 95 % CI [-6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (-0.36 mmol/L; 95 % CI [-1.04, 0.31]) in three RCTs, and triglycerides (TG) (-0.76 mmol/L; 95 % CI [-1.37, -0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (-0.97 mmol/L; 95 % CI [-1.18, -0.76]). CONCLUSIONS: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.

Effects of Astragalus membranaceus roots supplementation on growth performance, serum antioxidant and immune response in finishing lambs.

OBJECTIVE: Astragalus membranaceus root is a well-known traditional Chinese herbal medicine with many biological active constituents. This study was conducted to examine the effects of Astragalus membranaceus root powder (AMP) on growth performance, serum antioxidant and immune response in finishing lambs. METHODS: A total of thirty-six Guangling fat-tailed ram lambs (body weight = 19±2 kg, mean ±standard deviation) were randomly assigned to one of six treatments for a 40 d feeding period, with the first 10 d for adaptation. Treatments consisted of the lambs' basal diets with addition of 0, 5, 10, 15, 20, and 30 g/kg of diet of AMP. RESULTS: Response to supplementation level of AMP was quadratic (p≤0.032) for final weight and ADG with the greatest at 10 g/kg of diet, but dry matter intake was not affected (p≥0.227) by treatments. The increase of AMP supplementation resulted in a quadratic response in contents of triglyceride and creatinine (p<0.05), with the lowest values for 10 and 20 g/kg of diet, respectively. A linear and quadratic decrease was observed in activity of alkaline phosphatase in serum of lambs. As the AMP supplementation increased, the activities of total superoxide dismutase and total antioxidant capacity increased linearly (p≤0.018) and hydroxyl radical (OH-) decreased linearly (p = 0.002). For catalase (CAT) and malondialdehyde (MDA), quadratic (p≤0.001) effects were observed among treatments, with the greatest CAT and lowest MDA values at 10 g/kg AMP. Additionally, supplementing AMP up to a level of 10 or 15 g/kg of diet quadratically increased immunoglobulin and interleukin contents in the serum. CONCLUSION: The results indicated that AMP can be used as natural feed additive in the ration of lambs to improve ADG, antioxidant status, and immune functions, and the optimal dose was 10 g/kg of diet under the condition of this experiment.

[Effects of long term use of beclomethasone dipropionate nasal spray on bone density with perennial allergic rhinitis].

OBJECTIVE: To study the effects of long term use of beclomethasone dipropionate (BDP) nasal spray on bone density with perennial allergic rhinitis (AR) in adults. METHOD: A 5-year randomized study was conducted on the effects of BDP nasal spray on serum calcium, phosphorus, alkaline phosphatase, and bone density determined before and after the treatment in 36 adult patients with perennial AR. 20-45 years of age, were randomly divided into 3 groups. That is group A (nasal spray 1 - <3 year), group B (nasal spray BDP 3 - <5 year) and group C (nasal spray BDP > or =5 year). The data were analyzed by paired t test. RESULT: The perennial AR were followed up for more than > or =1 year, > or =3 year and > or =5 year to observe the influences of nasal spray BDP. There were no significant difference between the data examined before and after the treatment (P > 0.05). Bone development is not influenced by nasal spray BDP < or =400 microg/d within 5 years. CONCLUSION: Long term use of BDP nasal spray in adult patients does not lead to osteoporosis if the lowest effective steroid dose is given.