Icariin Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload Induced Dysfunction Through Mitochondrial Fusion and Fission, PI3K/AKT/mTOR and MAPK Pathways

Iron overload has been reported to contribute to bone marrow mesenchymal stem cells (BMSCs) damage, but the precise mechanism still remains elusive. Icariin, a major bioactive monomer belonging to flavonoid glucosides isolated from Herba Epimedii, has been shown to protect cells from oxidative stress induced apoptosis. The aim of this study was to investigate whether icariin protected against iron overload induced dysfunction of BMSCs and its underlying mechanism. In this study, we found that iron overload induced by 100 μM ferric ammonium citrate (FAC) caused apoptosis of BMSCs, promoted cleaved caspase-3 and BAX protein expressions while inhibited Bcl-2 protein expression, which effects were significantly attenuated by icariin treatment. In addition, iron overload induced significant depolarization of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and inhibition of mitochondrial fusion/fission, which effects were also attenuated by icariin treatment. Meanwhile, we found that iron overload induced by 100 μM FAC significantly inhibited mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, inhibited DRP1 and Cytochrome C protein translocation from the cytoplasm to mitochondria. Icariin at concentration of 1 μM was able to promote mitochondrial fission protein FIS1 and fusion protein MFN2 expressions, and increase DRP1 and cytochrome C protein translocation from the cytoplasm to mitochondria. Further, osteogenic differentiation and proliferation of BMSCs was significantly inhibited by iron overload, but icariin treatment rescued both osteogenic differentiation and proliferation of BMSCs. Further studies showed that icariin attenuated iron overload induced inactivation of the PI3K/AKT/mTOR pathway and activation of the ERK1/2 and JNK pathways. In summary, our study indicated that icariin was able to protect against iron overload induced dysfunction of BMSCs. These effects were potentially related to the modulation of mitochondrial fusion and fission, activation of the PI3K/AKT/mTOR pathway and inhibition of ERK1/2 and JNK pathways

Experimental study of boiling heat transfer characteristics of forced flow in annular tube under negative pressure

In order to investigate the recycling technology for efficiently recovering low-temperature wastewater waste heat from industrial production, we built an experimental device for forced boiling heat transfer in an annular tube. This paper takes a ring casing evaporator with an inner tube diameter of 30 mm, a length of 1450 mm, a wall thickness of 0.8 mm, and an outer tube diameter of 14.2 mm, which was used as the main object of study. We conducted experimental research on heat transfer in single-phase liquid flow and two-phase boiling phase change within annular tubes by varying the inlet circulating hot water temperature (60–85 °C), the mass flow rate of the circulating mass (0.85, 1.27, 1.69 kg m−2 s−1), and the inclination angle (0°–90°). The research results indicate that the heat transfer coefficient of boiling phase change within annular sleeves is significantly enhanced compared to convective heat transfer of single-phase liquid flow within annular tubes. This signifies that employing heat pipe technology for waste heat recovery can achieve highly efficient heat transfer processes. This study also reveals that with an increase in the inclination angle, the heat transfer coefficient on the boiling surface follows a trend of initial increase followed by a decrease. Near an inclination angle of 30° within the annular jacket tube, the heat transfer coefficient of two-phase boiling phase change reaches its maximum value. The findings of this study provide certain theoretical guidance for the application of heat pipe energy-saving technology in the field of medium- and low-temperature waste water recovery and utilization

Performance Study of Gravity-Type Heat Pipe Applied to Fuel Cell Heat Dissipation

A gravity-type heat pipe boiling characteristics test rig was constructed to solve the heat dissipation problem of fuel cells during operation. The boiling heat transfer characteristics of water in a parallel plate under negative pressure at different inclination angles and heat flow density input are investigated. The results show that: First, the gravity-type heat pipe can dissipate some heat and it is possible to use it for fuel cell heat dissipation. Second, with a certain range of heat flow density, the temperature of all parts of the plate is about 80 °C, with a small temperature difference, which is conducive to the safe operation of the fuel cell. Third, the heat flow density is in the range of 2222~3111 W·m−2, the temperature difference is large, and the outlet temperature is greater than 80 °C, which exceeds the operating temperature of the fuel cell, and the power-type heat pipe should be used for heat dissipation. Fourth, the average temperature of the plate placed at an inclination angle of 45°~60° is lower compared to other angles, and the temperature is evenly distributed. On the one hand, the conclusions reveal the characteristics of boiling heat exchange under negative pressure conditions of water inside the flat plate and, on the other hand, provide a reference for designing heat pipe systems for fuel cell heat dissipation

Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway

Objective: Osteoarthritis (OA) is a common disease with a complex pathology including mechanical load, inflammation, and metabolic factors. Chondrocyte ferroptosis contributes to OA progression. Because iron deposition is a major pathological event in ferroptosis, deferoxamine (DFO), an effective iron chelator, has been used to inhibit ferroptosis in various degenerative disease models. Nevertheless, its OA treatment efficacy remains unknown. We aimed to determine whether DFO alleviates chondrocyte ferroptosis and its effect on OA and to explore its possible mechanism.Methods: Interleukin-1β (IL-1β) was used to simulate inflammation, and chondrocyte ferroptosis was induced by erastin, a classic ferroptosis inducer. A surgical destabilized medial meniscus mouse model was also applied to simulate OA in vivo, and erastin was injected into the articular cavity to induce mouse knee chondrocyte ferroptosis. We determined the effects of DFO on ferroptosis and injury-related events: chondrocyte inflammation, extracellular matrix degradation, oxidative stress, and articular cartilage degradation.Results: IL-1β increased the levels of ROS, lipid ROS, and the lipid peroxidation end product malondialdehyde (MDA) and altered ferroptosis-related protein expression in chondrocytes. Moreover, ferrostatin-1 (Fer-1), a classic ferroptosis inhibitor, rescued the IL-1β–induced decrease in collagen type II (collagen II) expression and increase in matrix metalloproteinase 13 (MMP13) expression. Erastin promoted MMP13 expression in chondrocytes but inhibited collagen II expression. DFO alleviated IL-1β– and erastin-induced cytotoxicity in chondrocytes, abrogated ROS and lipid ROS accumulation and the increase in MDA, improved OA-like changes in chondrocytes, and promoted nuclear factor E2–related factor 2 (Nrf2) antioxidant system activation. Finally, intra-articular injection of DFO enhanced collagen II expression in OA model mice, inhibited erastin-induced articular chondrocyte death, and delayed articular cartilage degradation and OA progression.Conclusion: Our research confirms that ferroptosis occurs in chondrocytes under inflammatory conditions, and inhibition of chondrocyte ferroptosis can alleviate chondrocyte destruction. Erastin-induced chondrocyte ferroptosis can stimulate increased MMP13 expression and decreased collagen II expression in chondrocytes. DFO can suppress chondrocyte ferroptosis and promote activation of the Nrf2 antioxidant system, which is essential for protecting chondrocytes. In addition, ferroptosis inhibition by DFO injection into the articular cavity may be a new OA treatment

Meclizine Prevents Ovariectomy-Induced Bone Loss and Inhibits Osteoclastogenesis Partially by Upregulating PXR

Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast. In the present study, we explored the effect of meclizine on RANKL-induced osteoclastogenesis both in vivo and in vitro. In primary bone marrow-derived macrophages (BMMs), meclizine reduced osteoclast formation and bone resorption in a dose-dependent manner, while knockdown of PXR with siRNA partially abrogated the osteoclastogenesis inhibition of meclizine. On the one hand, at the molecular level, meclizine attenuated RANKL-induced activation of c-Fos, NFATc1, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs), including ERK and p38, but not JNK. Meanwhile, meclizine reduced the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. On the other hand, meclizine decreased OVX-induced bone loss by repressing osteoclast activity. In conclusion, our results indicated that meclizine inhibits osteoclastogenesis via regulation of several RANKL signaling pathways and PXR was involved in the processes. Therefore, meclizine may be considered as a novel therapeutic candidate for osteoclast-related diseases

Observational registry of basal insulin treatment in patients with type 2 diabetes in China: safety and hypoglycemia predictors

Background: The Observational Registry of Basal Insulin Treatment (ORBIT) study evaluated the safety of basal insulin (BI) in real-world settings in China. Methods: We analyzed 9002 patients with type 2 diabetes (T2D) inadequately controlled with oral hypoglycemic agents from 8 geographic regions and 2 hospital tiers in China who initiated and maintained BI treatment. Body weight and hypoglycemic episodes were recorded at baseline and 3 and 6 months. Serious adverse events (SAEs) were recorded at 3 and 6 months. Results: Age, gender, inpatient/outpatient status, body mass index, glycated hemoglobin (HbA1c) at baseline and at the end of study, T2D duration, microvascular complications, BI type, combination with insulin secretagogues, self-monitoring of blood glucose frequency, and insulin dosage, all predicted hypoglycemia. BI use generally did not induce significant weight gain (0.02kg); weight gain with insulin detemir (-0.30kg) was less than that with neutral protamine Hagedorn (NPH) insulin (0.20kg) or insulin glargine (0.05kg). Overall, general hypoglycemia incidence (5.6% vs. 7.7%) and annual event rate (1.6 vs. 1.8) were similar before and after BI initiation, whereas a slight decrease was noted in severe hypoglycemia incidence (0.6%-0.3%) and frequency (0.05-0.03 events/patient-year). The general hypoglycemia rate was lowest with insulin glargine, whereas there was no significant difference in severe hypoglycemia among the three BI groups. Overall, 3.5% of patients had at least one SAE during the study. Most SAEs were found to be unrelated to BI treatment. Conclusions: Real-world BI use, particularly insulin detemir and glargine, was associated with only slight weight gain and low hypoglycemia risk in patients with T2D in China

Ordered Assembly of NiCo₂O₄ Multiple Hierarchical Structures for High-Performance Pseudocapacitors

The design and development of nanomaterials has become central to the advancement of pseudocapacitive performance. Many one-dimensional nanostructures (1D NSs), two-dimensional nanostructures (2D NSs), and three-dimensional hierarchical structures (3D HSs) composed of these building blocks have been synthesized as pseudocapacitive materials via different methods. However, due to the unclear assembly mechanism of these NSs, reports of HSs simultaneously assembled from two or more types of NSs are rare. In this article, NiCo₂O₄ multiple hierarchical structures (MHSs) composed of 1D nanowires and 2D nanosheets are simply grown on Ni foam using an ordered two-step hydrothermal synthesis followed by annealing processing. The low-dimensional nanowire is found to hold priority in the growth order, rather than the high-dimensional nanosheet, thus effectively promoting the integration of these different NSs in the assembly of the NiCo₂O₄ MHSs. With vast electroactive surface area and favorable mesoporous architecture, the NiCo₂O₄ MHSs exhibit a high specific capacitance of up to 2623.3 F g^–1, scaled to the active mass of the NiCo₂O₄ sample at a current density of 1 A g^–1. A nearly constant rate performance of 68% is achieved at a current density ranging from 1 to 40 A g^–1, and the sample retains approximately 94% of its maximum capacitance even after 3000 continuous charge–discharge cycles at a consistently high current density of 10 A g^–1

Characterization of Fecal Microbiota across Seven Chinese Ethnic Groups by Quantitative Polymerase Chain Reaction

<div><p>The human gut microbiota consists of complex microbial communities, which possibly play crucial roles in physiological functioning and health maintenance. China has evolved into a multicultural society consisting of the major ethnic group, Han, and 55 official ethnic minority groups. Nowadays, these minority groups inhabit in different Chinese provinces and some of them still keep their unique culture and lifestyle. Currently, only limited data are available on the gut microbiota of these Chinese ethnic groups. In this study, 10 major fecal bacterial groups of 314 healthy individuals from 7 Chinese ethnic origins were enumerated by quantitative polymerase chain reaction. Our data confirmed that the selected bacterial groups were common to all 7 surveyed ethnicities, but the amount of the individual bacterial groups varied to different degree. By principal component and canonical variate analyses of the 314 individuals or the 91 Han subjects, no distinct group clustering pattern was observed. Nevertheless, weak differences were noted between the Han and Zhuang from other ethnic minority groups, and between the Heilongjiang Hans from those of the other provinces. Thus, our results suggest that the ethnic origin may contribute to shaping the human gut microbiota.</p></div