Osteogenic differentiation of bone mesenchymal stem cells on linearly aligned triangular micropatterns.

Mesenchymal stem cells (MSCs) hold promise for regenerative medicine, particularly for bone tissue engineering. However, directing MSC differentiation towards specific lineages, such as osteogenic, while minimizing undesired phenotypes remains a challenge. Here, we investigate the influence of micropatterns on the behavior and lineage commitment of rat bone marrow-derived MSCs (rBMSCs), focusing on osteogenic differentiation. Linearly aligned triangular micropatterns (TPs) and circular micropatterns (CPs) coated with fibronectin were fabricated to study their effects on rBMSC morphology and differentiation and the underlying mechanobiological mechanisms. TPs, especially TP15 (15 µm), induced the cell elongation and thinning, while CPs also promoted the cell stretching, as evidenced by the decreased circularity and increased aspect ratio. TP15 significantly promoted osteogenic differentiation, with increased expression of osteogenic genes (Runx2, Spp1, Alpl, Bglap, Col1a1) and decreased expression of adipogenic genes (Pparg, Cebpa, Fabp4). Conversely, CPs inhibited both osteogenic and adipogenic differentiation. Mechanistically, TP15 increased Piezo1 activity, cytoskeletal remodeling including the aggregates of F-actin and myosin filaments at the cell periphery, YAP1 nuclear translocation, and integrin upregulation. Piezo1 inhibition suppressed the osteogenic genes expression, myosin remodeling, and YAP1 nuclear translocation, indicating Piezo1-mediated the mechanotransduction in rBMSCs on TPs. TP15 also induced osteogenic differentiation of BMSCs from aging rats, with upregulated Piezo1 and nuclear translocation of YAP1. Therefore, triangular micropatterns, particularly TP15, promote osteogenesis and inhibit adipogenesis of rBMSCs through Piezo1-mediated myosin and YAP1 pathways. Our study provides novel insights into the mechanobiological mechanisms governing MSC behaviors on micropatterns, offering new strategies for tissue engineering and regenerative medicine.

Syndecan-1 as a predictor of vulnerable atherosclerotic plaques.

Aims: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model. Methods and results: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group's plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability. Conclusion: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes.

Harnessing Mitochondrial Stress for Health and Disease: Opportunities and Challenges.

Mitochondria, essential organelles orchestrating cellular metabolism, have emerged as central players in various disease pathologies. Recent research has shed light on mitohormesis, a concept proposing an adaptive response of mitochondria to minor disturbances in homeostasis, offering novel therapeutic avenues for mitochondria-related diseases. This comprehensive review explores the concept of mitohormesis, elucidating its induction mechanisms and occurrence. Intracellular molecules like reactive oxygen species (ROS), calcium, mitochondrial unfolded proteins (UPRmt), and integrated stress response (ISR), along with external factors such as hydrogen sulfide (H2S), physical stimuli, and exercise, play pivotal roles in regulating mitohormesis. Based on the available evidence, we elucidate how mitohormesis maintains mitochondrial homeostasis through mechanisms like mitochondrial quality control and mitophagy. Furthermore, the regulatory role of mitohormesis in mitochondria-related diseases is discussed. By envisioning future applications, this review underscores the significance of mitohormesis as a potential therapeutic target, paving the way for innovative interventions in disease management.

Zinc and sulfur functionalized biochar as a peroxydisulfate activator via deferred ultraviolet irradiation for tetracycline removal.

To enhance the degradation of tetracycline class (TC) residuals of high-concentration from pharmaceutical wastewater, a novel zinc (Zn) and sulfur (S) functionalized biochar (SC-Zn), as a peroxydisulfate (PDS) activator, was prepared by two-step pyrolysis using ZnSO4 accumulated water-hyacinth. Results showed that the removal rate of 50, 150, and 250 mg per L TC reached 100%, 99.22% and 94.83% respectively, by the SC-Zn/PDS system at a dosage of 0.3 g per L SC-Zn and 1.2 mM PDS, via the deferred ultraviolet (UV) irradiation design. Such excellent performance for TC removal was due to the synergetic activation of PDS by the biochar activator and UV-irradiation with biochar as a responsive photocatalyst. The functionalization of the co-doped Zn and S endowed the biochar SC-Zn with a significantly enhanced catalytic performance, since Zn was inferred to be the dominant catalytic site for SO4˙- generation, while S played a key role in the synergism with Zn by acting as the primary adsorption site for the reaction substrates. The employed SC-Zn/PDS/UV system had excellent anti-interference under different environmental backgrounds, and compared with the removal rate of TC by adsorption of SC-Zn, the increasing rate in the SC-Zn/PDS/UV system (18.75%) was higher than the sum of the increases in the SC-Zn/PDS (9.87%) and SC-Zn/UV systems (3.34%), furtherly verifying the systematic superiority of this synergy effect. This study aimed to prepare a high-performance functionalized biochar activator and elucidate the rational design of deferred UV-irradiation of PDS activation to efficiently remove high-concentration antibiotic pollutants.

Modulation of muscarinic receptors by anisodine hydrobromide in cerebral ischemia.

Ischemic cerebrovascular diseases pose significant challenges due to their high mortality, disability rates, and recurrence risk, imposing substantial societal and healthcare burdens. Current treatment modalities, including medication and surgical interventions, have limitations. This study explores the therapeutic potential of anisodine hydrobromide, a neuroprotective compound, with a focus on its interaction with muscarinic receptors (M1-M5) in cerebral ischemic diseases, employing a middle cerebral artery occlusion (MCAO) rat model, and microglial HM cells and astrocytes SVG12 as models. Immunohistochemistry comprehensively assessed M1-M5 receptor expression in cerebral arteries, hippocampus, and parenchymal tissues in MCAO rats before and after anisodine hydrobromide administration. Additionally, a hypoxia/reoxygenation (H/R) model validated our findings using SVG12 and HM cells. M receptor mechanisms under hypoxia, including calcium ion influx, reactive oxygen species (ROS) levels, and aspartate expression were explored. Anisodine hydrobromide effectively reduced exacerbated M1, M2, M4, and M5 receptor expression in hypoxia/reoxygenation (H/R)-treated brain tissues and M2 receptors in H/R-treated cells. Concentration-dependent inhibition of calcium ion influx and ROS levels was observed, elucidating its neuroprotective mechanisms. Under H/R conditions, HM cells exhibited decreased aspartate levels by anisodine hydrobromide, Atropine, and M2 inhibitor treatments. These findings shed light on the modulation of muscarinic receptors, particularly the M2 subtype, by anisodine hydrobromide in cerebral ischemia. The neuroprotective effects observed in this study highlight the promising clinical prospects of anisodine hydrobromide as a potential therapeutic agent for ischemic brain diseases, warranting further investigation into its mechanisms of action.

Significant Improvement of Adsorption for Phosphate Removal by Lanthanum-Loaded Biochar.

Due to eutrophication, removing phosphate ions from wastewater has received a lot of attention. In order to improve the phosphorus adsorption capacity of the material, this study used biomass pyrolysis to create a series of biochars modified with metal chloride ions. In accordance with adsorption tests, lanthanum-loaded biochar (LCBC) had a significant phosphorus adsorption capacity of approximately 666.67 mg/g, which was 30 times greater than that of pristine biochar. Adsorption kinetic analysis revealed that the LCBC's adsorption process could be fitted to the pseudo-secondary kinetic equation, indicating that chemical processes were primarily responsible for controlling the adsorption process. Zeta potential, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis showed that the main adsorption mechanism of LCBC for phosphate removal was electrostatic attraction of protonated H+ with negatively charged mono-hydrogen phosphate and dihydrogen phosphate ions and complexation reaction of the C=O on the carboxyl group and P=O on the phosphate group with the oxygen on the phosphate group and hydroxyl group. According to regeneration performance results, LCBC performed relatively better than as-prepared adsorbents, and the phosphate removal rate was approximately 75.1% after the fifth regeneration cycle. The study provided a potential approach for creating and preparing an adsorbent with high adsorption for phosphate removal.

Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice.

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.

Behaviors Related to Psychiatric Disorders and Pain Perception in C57BL/6J Mice During Different Phases of Estrous Cycle.

Robust sex difference among humans regarding psychiatry- and pain-related behaviors is being researched; however, the use of female mice in preclinical research is relatively rare due to an unchecked potential behavioral variation over the estrous cycle. In the present study, a battery of psychiatry- and pain-related behaviors are examined under physiological condition in female C57BL/6J mice over different estrous cycle phases: proestrus, estrous, metestrous, diestrous. Our behavioral results reveal that there is no significant difference over different phases of the estrous cycle in social interaction test, sucrose preference test, tail suspension test, open field test, marble burying test, novelty-suppressed feeding test, Hargreaves thermal pain test, and Von Frey mechanical pain test. These findings implicate those psychiatry- and pain-related behaviors in normal female C57BL/6J mice appear to be relatively consistent throughout the estrous cycle; the estrous cycle might not be a main contributor to female C57BL/6J mice's variability of behaviors.