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Bone metastasis is the prevalent form of metastasis in breast cancer, resulting in severe pain, pathological fractures, nerve compression, hypercalcemia, and other complications that significantly impair patients' quality of life. The infiltration and colonization of breast cancer (BC) cells in bone tissue disrupt the delicate balance between osteoblasts and osteoclasts within the bone microenvironment, initiating a vicious cycle of bone metastasis. Once bone metastasis occurs, conventional medical therapy with bone-modifying agents is commonly used to alleviate bone-related complications and improve patients' quality of life. However, the utilization of bone-modifying agents may cause severe drug-related adverse effects. Plant-derived natural products such as terpenoids, alkaloids, coumarins, and phenols have anti-tumor, anti-inflammatory, and anti-angiogenic pharmacological properties with minimal side effects. Certain natural products that exhibit both anti-breast cancer and anti-bone metastasis effects are potential therapeutic agents for breast cancer bone metastasis (BCBM). This article reviewed the effects of plant-derived natural products against BCBM and their mechanisms to provide a reference for the research and development of drugs related to BCBM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Aims: Momordica charantia L. ( M. charantia ) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM., Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals., Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: -0.85 mmol/L; 95%CI: -1.44, -0.26; p  = 0.005; I 2  = 73.4 %), postprandial glucose (PPG) (WMD: -2.28 mmol/L; 95%CI: -3.35, -1.21; p  = 0.000; I 2  = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.38 %; 95%CI: -0.53, -0.23; p  = 0.000; I 2  = 37.6 %), and total cholesterol (TC) (WMD: -0.38 mmol/L; 95%CI: -0.70, -0.07; p  = 0.017; I 2  = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)., Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Stachydrine is a hydrophilic quaternary amine salt with good antitumor effect, but its application is limited due to its rapid metabolism and low bioavailability. We synthesized and evaluated nine prodrugs of stachydrine, which showed suitable hydrophobicity (CLogP: -2.58-4.78, vs SS-0: -3.32) and better in vitro anticancer activity (IC 50 : 0.34 μM-14.03 mM, vs SS-0: 38.97 mM-147.19 mM) in comparison with stachydrine. Among them, SS-12, SS-16 and SS-18 are the most effective compounds against 4T1 cells, and the IC 50 is 2.15-24.14 μM. Especially, compared with stachydrine, SS-12 significantly blocked the cell cycle in the G0/G1 phase, reduced the mitochondrial membrane potential, and induced the apoptosis of 4T1 cells through mitochondria pathway, which increased the expressions of Bax and cleaved caspase-3 protein, decrease the expression of Bcl-2. The pharmacokinetics of SS-12 showed a rational bioavailability (79.6%), and a longer retention time (T 1/2  = 7.62 h) than that of stachydrine (T 1/2  ≈ 1.16 h) in rats. Compared with stachydrine, SS-12 significantly enhanced the anticancer efficacy (56.32% of tumor-inhibition rates, vs SS-0: 3.89%), meanwhile, ameliorated the tumor-induced organ damage in mice. Therefore, SS-12 may be a promising prodrug of stachydrine against breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Postmenopausal osteoporosis (PMOP) is a chronic bone metabolic disease, which often causes fractures and various complications, it causes a great social and economic burden, and it is urgent to use modern research techniques to elucidate the pathogenesis of PMOP. At the same time, because of the complex physiological and pathological interaction mechanism between osteoporosis and sarcopenia, the correlation research has become a hot topic. Ovary removal is a commonly used experimental method to study the endocrine system of female animals, and it is also the best animal model to study PMOP. In this study, the preparation of the ovariectomized rat was confirmed through the detection of vaginal smear, the level of bone formation markers, and the analysis of bone tissue morphology. Transcriptome sequencing was used to analyze the molecular mechanism of PMOP in ovariectomized rats, qRT-PCR was used to verify the key targets. Results of Micro-CT and scanning electron microscopy (SEM) showed that the trabecular structure was disorganized and the symptoms of osteoporosis appeared, this indicating that the ovariectomized rats model was successfully prepared. Transcriptional sequencing results of femur tissue showed that 452 differentially expressed genes (DEGs) were screened. Bioinformatics analysis results showed that the osteoporosis caused by ovariectomized rats was mainly related to muscle contraction, calcium signaling pathway, etc. Results of qRT-PCR were consistent with transcriptome analysis. These results reveal the pathogenesis of PMOP in ovariectomized rats and also offer a possibility for elucidating the relevance of action between PMOP and sarcopenia.

Purpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats., Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue., Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-β1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney., Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Tian et al.)

Background: Chronic ankle instability (CAI) is a form of musculoskeletal disease that can occur after a lateral ankle sprain, and it is characterized by pain, recurrent ankle sprains, a feeling of "giving way" at the ankle joint, and sensorimotor deficits. There has been increasing evidence to suggest that plastic changes in the brain after the initial injury play an important role in CAI. As one modality to treat CAI, whole-body vibration (WBV) has been found to be beneficial for treating the sensorimotor deficits accompanying CAI, but whether these benefits are associated with brain plasticity remains unknown. Therefore, the current study aims to investigate the effect of WBV on sensorimotor deficits and determine its correlation with plastic changes in the brain., Methods: The present study is a single-blind randomized controlled trial. A total of 80 participants with CAI recruited from the university and local communities will be divided into 4 groups: whole-body vibration and balance training (WBVBT), balance training (BT), whole-body vibration (WBV), and control group. Participants will be given the WBV intervention (25-38 Hz, 1.3-2 mm, 3-time per week, 6-week) supervised by a professional therapist. Primary outcome measures are sensorimotor function including strength, balance, proprioception and functional performance. Brain plasticity will be evaluated by corticomotor excitability, inhibition, and representation of muscles, as measured by transcranial magnetic stimulation. Activation of brain areas will be assessed through functional near-infrared spectroscopy. Secondary outcome measures are self-reported functional outcomes involving the Cumberland Ankle Instability Tool and the Foot and Ankle Ability Measure. All tests will be conducted before and after the WBV intervention, and at 2-week follow-up. Per‑protocol and intention-to-treat analysis will be applied if any participants withdraw., Discussion: This is the first trial to investigate the role of brain plasticity in sensorimotor changes brought by WBV for individuals with CAI. As plastic changes in the brain have been an increasingly important aspect in CAI, the results of the current study can provide insight into the treatment of CAI from the perspective of brain plasticity., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300068972); registered on 02 March 2023., (© 2023. The Author(s).)

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Liu et al.)

Emerging evidence revealed that participating in sports may have benefits for health, but the association between sports participation and self-rated overall health has not been clearly established in children and adolescents. The present study aimed to examine the cross-sectional relationships between sports participation and self-rated overall health. A national sample of 42,777 (mean age = 9.4 ± 5.2, 48.3% girls) United States children and adolescents completed self-administered questionnaires and were included in the final analysis. The crude and adjusted odds ratio (ORs) and 95% CI were used to analyze the association between sports participation and self-rated overall health. Results indicated that children and adolescents participated in sports were more likely to report better overall health (OR = 1.92, 95%CI: 1.83, 2.02) compared to those not participating in sports. This study found that sport participation was positively associated with self-rated overall health in children and adolescents. This study offers evidence concerning adolescents' health literacy promotion., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

Objective: The purpose of this research was to investigate the prevalence of lifestyle behaviors and suicide-related behaviors and the association between them using a nationally representative sample of adolescents from the USA. Methods: 13,677 high school students aged 14-18 years were included in this cross-sectional study. The research data were retrieved from the Youth Risk Behavior Surveillance System Survey in 2019. All data on age, sex, grade, race, physical activity, television time, fruit intake, and suicide-related behavior were self-reported by students. Logistic regression models were adopted to examine the association between lifestyle behaviors and the suicide-related behaviors. Results: Students who played video/computer games for ≥2 h had higher risk of suicide attempt (OR = 1.55, 95%CI: 1.30-1.85). Daily sleep duration of ≤8 h was positively associated with considering a suicide attempt (OR = 1.99, 95%CI: 1.62-2.43). In addition, participants who did not engage in any sport team were more likely to report considering a suicide attempt (OR = 1.50, 95%CI: 1.24-1.81). Conclusion: This research suggests that some lifestyle behaviors (e.g., time for video or computer use, sleep duration, sports team participation, regular breakfast intake, and substance use) are associated with increased risk of suicidal behavior and ideation in high school students. To identify the specific effect of multiple lifestyle factors in influencing the risk of suicide-related behaviors in high school students, longitudinal studies are warranted in future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chi, Taylor, Chen, Memon, Zhang, Song, Li, Luo and Zou.)

Objective: To observe the brain protective effect of Leonuri Herba Total Alkali (LHA) on cerebral ischemia reperfusion injury in rats, so as to provide basis for clinical research., Methods: Adult male SD rats were randomly assigned into sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, and LHA + MCAO/R group (25 mg/kg, 50 mg/kg, and 100 mg/kg). Fourteen days before MCAO/R surgery, the rats in treatment groups were orally administered with LHA in ultrapure water once daily for 14 days, while rats in the sham and MCAO groups were given the same amount of saline in advance. After 1 h of administration on the 14th day, MCAO surgery was subjected. The neurological deficits, brain infarct volume, histopathology, immunofluorescence, inflammation indicators and the gene/protein expressions of BDNF-TrKB-PI3K/Akt signaling pathway in the rat brain tissue were evaluated 24 h after the MCAO/R-injury., Results: It was found that rats in LHA pre-administration group showed significantly reduced neurological deficit scores, infarction volume, the serum levels of NSE and S100β. Meanwhile, the content of Evans Blue (EB) in brain tissue from LHA group was decreased, as well as the levels of inflammatory cytokines and their gene levels. Moreover, LHA pre-administration inhibited the expression of CD44, GFAP, FOXO1 and promoted the expression of BDNF and NeuN. In addition, LHA pre-administration could up-regulate the protein expression of TrkB, p-PI3K, p-Akt, Bcl-2, and down-regulate the protein expression of Bax, and increase the level of Bcl-2/Bax., Conclusions: The study demonstrated that LHA pre-administration could regulate the PI3K/Akt pathway by increasing BDNF levels, and play a neuroprotective role in cerebral ischemia-reperfusion injury., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)