To evaluate the short term effect of zoledronic acid on bone remodeling in the streptozotocin induced diabetes rats.Diabetes was induced by an injection of streptozotocin (60 mg/kg). The rats were treated with zoledronic acid (0.1 mg/kg) at the onset of diabetes (Z-I group) and 2 weeks later (Z-II group). Rats were sacrificed at the 1, 2, 3, 4 and 5 weeks after the onset of diabetes. Real-time PCR and western blot were performed to detect the expression of the following osteogenic gene mRNAs and their proteins: bone morphogenetic proteins 2 (BMP2), Runx2, Osterix and Noggin. The bone mineral density (BMD) and the mechanical resistance test was measured.BMP2, Runx2 and Osterix mRNA and protein expression in group D had regulated down, while Noggin expression increased. Z-I treatment could reverse the results. However group Z-II showed only a transient reversing effect. On the 5th week in group D, the BMD decreased, the bone trabecular distance increased, while the trabecular thickness and bone trabecular volume were reduced, the biomechanics index decreased significantly. Zoledronic acid treatment restored these alterations.Zoledronic acid administered in the early stage of the diabetes could prevent the osteopenia. The underlying mechanisms might be that zoledronic acid treatment reversed the effect of diabetes on the expression of osteoblast-regulating transcription factors: BMP2, Runx2 and Osterix.
We aimed to evaluate the effect of red meat diet on gut microbiota in mice. Balb/c mice at weaning were randomized into control group and red meat groups with different proportions (25%, 50%, and 75%). Mice were fed with a standard pellet diet as control group, while those were fed with different proportions of red meat diet as red meat groups. After 8 weeks, they were sacrificed and their intestinal contents were obtained for 16S rRNA sequencing and bioinformatics analysis. Our results showed that there were significant-structural differences among the four groups. The top-two most abundant phylum were Firmicutes and Bacteroidetes. In the red meat groups, the abundance of Bacteroidetes was increased, but the abundance of Firmicutes was decreased. At the family level, Bacteroidaceae and Family XIII were significantly higher in the high-dose group than those in the control group. There were also significant differences in abundance of many genera. In conclusion, different proportions of red meat diet may lead to changes in gut microbial flora in mice. These changes may be pathological and may be related to the frequent occurrence of many diseases.
AbstractBackground The fibrinogen to albumin ratio (FAR) is a novel inflammatory indicator correlating with the severity of coronary artery disease. An indicator of atherosclerosis is the Castelli Risk Index 2 (CI2 = LDL-C/HDL-C). Yet, little research has focused on the link between both of indicators and coronary artery disease (CAD) and carotid atherosclerotic lesions in distinct glucose metabolic states. Thus, the aim of this investigation was to look into the link involving these two indicators and atherosclerotic lesions of the coronary and carotid arteries in patients with CAD who were in distinct glucose metabolic states. Method: In this investigation, coronary angiography and carotid Doppler ultrasonography were performed about 2825 individuals suffering from symptomatic CAD at Tianjin Union Medical Center from 2016 to 2023.The number of stenotic arteries in the coronary arteries was counted. Both the Carotid intima-media thickness and the Gensini score were taken into account or computed. Normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM) were the three categories of glucose status according to the WHO diabetes guidelines. Patients were also divided into FAR index and Castelli risk index 2 quartiles to look into the link between FAR index and Castelli risk index 2 and coronary or carotid artery lesions in CAD patients with different glucose metabolic states. Receiver operating characteristic (ROC) curves were constructed to analyse the predictive value of the FAR index and Castelli risk index for coronary artery severity and carotid artery lesions. Result According to logistic regression analysis, the FAR index and Castelli risk index 2 were statistically associated with coronary artery disease and carotid plaques (P< 0.05). The FAR index was linked with CAD severity regardless of glucose metabolism states (P < 0.05). It was also substantially associated with carotid lesions in the NGR and Pre-DM stages (P < 0.05), but not in the DM state (P < 0.05). The Castelli risk index 2 was strongly linked with CAD severity and carotid artery lesions in both NGR and DM status (P< 0.05). Yet, there was no statistical significance in Pre-DM states. (P> 0.05). The FAR index and Castelli risk index 2 exhibited higher regions underneath the ROC curve in forecasting coronary artery lesions and carotid atherosclerosis. Conclusion The FAR index and Castelli risk index 2 were significantly associated with coronary and carotid atherosclerosis in different glucose metabolic states. FAR index and Castelli risk index 2 have predictive value for coronary artery lesions and carotid plaques.
Solasodine glycosides, such as solamargine, have been proved to be very important anti-cancer agents. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides 2-9 were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3 cells) were evaluated by MTT assays. The results indicated that compounds 2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and 1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism tests demonstrated that these compounds could induce apoptosis detected by DAPI staining, and Annexin V and propidium iodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at the G2/M phase when exposure to these compounds was examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.
Spinal cord injury (SCI) can result in irreversible sensory and motor disability with no effective treatment currently. After SCI, infiltrated macrophages accumulate in epicenter through destructed blood-spinal cord barrier (BSCB). Further, great majority of macrophages are preferentially polarized to M1 phenotype, with only a few transient M2 phenotype. The purpose of this study was to explore roles of vascular endothelial cells in microglia/macrophages polarization and the underlying mechanism. Lipopolysaccharide (LPS) was used to pretreat BV2 microglia and RAW264.7 macrophages followed by administration of conditioned medium from microvascular endothelial cell line bEnd.3 cells (ECM). Analyses were then performed to determine the effects of exosomes on microglia/macrophages polarization and mitochondrial function. The findings demonstrated that administration of ECM shifted microglia/macrophages towards M2 polarization, ameliorated mitochondrial impairment, and reduced reactive oxygen species (ROS) production in vitro. Notably, administration of GW4869, an exosomal secretion inhibitor, significantly reversed these observed benefits. Further results revealed that exosomes derived from bEnd.3 cells (Exos) promote motor rehabilitation and M2 polarization of microglia/macrophages in vivo. Ubiquitin-specific protease 13 (USP13) was shown to be significantly enriched in BV2 microglia treated with Exos. USP13 binds to, deubiquitinates and stabilizes the NF-κB inhibitor alpha (IκBα), thus regulating microglia/macrophages polarization. Administration of the selective IκBα inhibitor betulinic acid (BA) inhibited the beneficial effect of Exos in vivo. These findings uncovered the potential mechanism underlying the communications between vascular endothelial cells and microglia/macrophages after SCI. In addition, this study indicates exosomes might be a promising therapeutic strategy for SCI treatment.
Purpose: To investigate the correlation between corneal biomechanical characteristics and refractive status in adolescents aged 5-13 years. Methods: A cross-sectional study involved 339 children aged 5-13 with a spherical equivalent (SE) range from -6.00 to +2.00 diopters. Axial length (AL) was measured by IOL Master, corneal biomechanical parameters by Corvis ST, and anterior segment parameters by Pentacam. According to SE of right eye, the subjects were divided into moderate myopia, mild myopia, and emmetropia group. The correlation between AL and SE and corneal biomechanical parameters was analyzed. The corneal biomechanical parameters of the three groups were also compared. Results: The A2V value in the moderate myopia group was significantly lower than that in both the mild group and emmetropia group (p < 0.001). PD in the moderate group was higher than that in the mild group (p < 0.05), while PD in mild myopia was higher than that in emmetropia (p < 0.05). The SSI in the emmetropia group was significantly higher than that in the other two groups (all p < 0.001), and the SSI in the mild group was higher than that in the moderate group (p < 0.01). The A2V value in the 11-13 years old group was lower than that in the 5-7 years old group (p < 0.001) and 8-10 years old group (p < 0.01). PD in the 11-13 years old group was significantly higher than that in the 8-10 years old group (p < 0.001), and PD in the 8-10 years old group was significantly higher than that in the 5-7 years old group (p < 0.01). The SSI in the 5-7 years old group was significantly higher than that in the 8-10 years old group (p < 0.001), and the SSI in the 8-10 years old group was significantly higher than that in the 11-13 years old group (p < 0.05). AL was positively correlated with PD and negatively correlated with SSI and A2V. SE was positively correlated with A2V and SSI and negatively correlated with PD. Conclusions: Corneal stiffness seems to decrease with the increase of SE. The changes of SSI, PD, and A2V were statistically significant and can be predictors of myopia progression in adolescents aged 5-13 years.
Abstract Background Whether iron intake can affect cardiovascular disease (CVD) and dyslipidemia is controversial. However, few studies have focused on reducing the risk of CVD in people at risk for dyslipidemia. This study explored the linear relationship and possible nonlinear relationship between CVD and dyslipidemia. Methods Dietary data were obtained from the China Health and Nutrition Survey between 2004 and 2015. The survey included 8173 participants older than 18 years. CVD risk was estimated by the Framingham risk score (FRS). Logistic regression analysis was used to determine whether iron intake affects CVD incidence and lipid profiles. The nonlinear association was tested with restricted cubic splines (RCSs). Results For males, higher total iron intake [the fifth quintile (Q) vs. Q1 odds ratio (OR): 0.335, 95% confidence interval (CI): 0.248–0.453], heme iron intake (OR: 0.679, 95% CI: 0.492–0.937) and non-heme iron intake (OR: 0.362, 95% CI: 0.266–0.492) reduced CVD incidence. Heme iron intake increased high low-density lipoprotein cholesterol (LDL-C) (OR: 1.786, 95% CI: 1.226–2.602), high total cholesterol (TC) (OR: 2.404, 95% CI: 1.575–3.669), high triglyceride (TG) (OR: 1.895, 95% CI: 1.423–2.523), and low apolipoprotein A1/apolipoprotein B (ApoA-1/ApoB) risk (OR: 1.514, 95% CI: 1.178–1.945). Moderate non-heme iron intake reduced high-density lipoprotein cholesterol (HDL-C) incidence (Q5 vs. Q1 OR: 0.704, 95% CI: 0.507–0.979). For females, higher total iron intake (Q5 vs. Q1 OR: 0.362, 95% CI: 0.266–0.492) and non-heme iron intake (OR: 0.347, 95% CI: 0.154–0.781) reduced CVD incidence. Heme iron intake increased high LDL-C (OR: 1.587, 95% CI: 1.160–2.170) and high TC incidence (OR: 1.655, 95% CI: 1.187–2.309). Conclusions Men, especially those at risk of developing dyslipidemia, should consume non-heme rather than heme iron to reduce CVD incidence. For women, increased heme iron intake did not reduce CVD incidence. Therefore, women should minimize their heme iron intake to prevent dyslipidemia.
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