Inhibition of miR-665 alleviates neuropathic pain by targeting SOCS1

Purpose: To investigate the effect of miR-665 in neuropathic pain and the possible molecular mechanism involved.Methods: A neuropathic pain model was established using chronic constriction injury (CCI) methods in Sprague Dawley (SD) rats. Mechanical and thermal hyperalgesia were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), respectively. The inflammation response was determined by assessing the production of inflammation factors. The target relationship of miR-665 and suppressor of cytokine signaling 1 (SOCS1) was verified by luciferase assay.Results: In the CCI rat model, PWT and PWL decreased following treatment with miR-665 (p < 0.01). MiR-665 was elevated in the spinal cord and microglia of CCI rats at different time points (p < 0.01). Down-regulation of miR-665 increased PWT and PWL and inhibited the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in CCI rats (p < 0.01). Luciferase assay results indicate that SOCS1 was the target of miR-665 (p < 0.01). SOCS1 decreased in CCI rats (p < 0.01) after treatment with miR-665. MiR-665 negatively regulated the expression of SOCS1 (p < 0.01). Down-regulation of SOCS1 reversed the alleviating effect of decreased miR-665 on pain sensitivity and inflammationresponse (p < 0.01).Conclusion: Down-regulation of miR-665 alleviates neuropathic pain by targeting SOCS1, and hence making miR-665 a promising therapeutic target for neuropathic pain. Keywords: MiR-665, SOCS1, Neuropathic pain, CCI, Spinal cor

Melatonin reverses type 2 diabetes-induced cognitive deficits via attenuation of oxidative/nitrosative stress and NF-κB-mediated neuroinflammation in rat hippocampus

Purpose: To evaluate the protective effect of melatonin on diabetes-induced cognitive dysfunction. Methods: Rats were fed a high-fat diet + streptozotocin (HFD + STZ) for 15 weeks to induce type 2 diabetes (HFD + STZ group). At the end of the 15-week induction of diabetes, cognitive function in the diabetic rats was estimated using a Morris water maze and an object recognition task. Next, the diabetic rats were treated with melatonin (10 mg/ kg, po) for 3 weeks. Thereafter, cognitive function was reevaluated in the melatonin-treated diabetic rats (melatonin group). Results: There was a significant (p < 0.01) decrease in the serum glucose and insulin in melatonintreated diabetes type 2 rats compared with that of diabetes type 2 rats exposed to only HFD + STZ. Treatment with melatonin (10 mg/kg, po) for 3 weeks in diabetic type 2 rats also caused a significant increase (p < 0.01) in the time spent in the target quadrant and preference index in diabetic rats compared with the HFD + STZ group. There were significant decreases in reactive oxygen species (ROS), oxido-nitrosative stress markers, including thiobarbituric acid reactive substances (TBARS), nitrite, and depleted glutathione (GSH) level in the hippocampus of melatonin-treated group, compared with the HFD + STZ-treated group. Moreover, the melatonin-treated group showed significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and reduction in the levels of proinflammatory cytokines. Conclusion: The results demonstrate that melatonin prevents cognitive dysfunction in type 2 diabetic rats by attenuating oxido-nitrosative stress and NF-κB-mediated neuroinflammation. This effect suggests that melatonin may be useful for the management of cognitive dysfunction in patients suffering from diabetes. Keywords: Cognitive dysfunction, Melatonin, Neuroinflammation, Nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), Oxido-nitrosative stress, Type 2 diabete

Conservation and diversification of the miR166 family in soybean and potential roles of newly identified miR166s

Identity between pre-miR166s in soybean. (TIF 5906 kb

The Protective Effect of Yi Shen Juan Bi Pill in Arthritic Rats with Castration-Induced Kidney Deficiency

Androgens have been linked to the onset, severity, and progression of rheumatoid arthritis (RA). In traditional Chinese medicine (TCM), the most common pattern in RA is kidney deficiency, which partly corresponds to a low sex hormone state. In this study, TCM kidney deficiency was induced in male Sprague-Dawley rats with castration surgery, and a TCM preparation, Yi Shen Juan Bi Pill (YJB), was used to treat collagen induced arthritis (CIA) rats with castration. Metabolomic technique was used to evaluate the pharmacological mechanism in castrated CIA rats treated by YJB. The results showed that castration significantly increased the severity of the arthritis in rats but was ameliorated by YJB. Its pharmacological mechanism was partially associated with lipid metabolites involving free fatty acid (FFA) and lysophosphatidylcholine (LPC). In conclusion, the experimental results demonstrate the protective effect of YJB on the TCM kidney deficiency pattern induced by androgen deficiency in CIA rats and support that YJB should be used for the clinical treatment of RA with TCM kidney deficiency pattern

Effects of Fe on microstructures and mechanical properties of Ti-15Nb-25Zr-(0, 2, 4, 8)Fe alloys prepared by spark plasma sintering

Biomedical Ti-15Nb-25Zr-(0, 2, 4, 8)Fe (mol%) alloys are prepared by mixing pure element powders and spark plasma sintering (SPS). Specimens with diameters of 20 mm and thicknesses of 3 mm are obtained by sintering at 1000°C for 10 min followed by cooling in the furnace. Some of the specimens are then heat-treated at 900°C for 1 h followed by water quenching. Zr and Fe are dissolved in Ti; however, segregation of Nb is observed in all of the alloys. The β and α′′ phases are observed in the as-sintered and heat-treated specimens owing to the insufficient diffusion of the alloying elements. Fe stabilizes the β phase and provides a solution-strengthening effect. With the increase in the Fe content in the as-sintered specimen, the compressive strength and micro-Vickers hardness are improved in the Ti-15-Nb-25Zr-(0, 2, 4)Fe alloys and slightly decreased in Ti-15-Nb-25Zr-8Fe. The as-sintered Ti-15Nb-25Zr-4Fe alloy exhibits the maximum compressive strength of 1740 MPa. Although the plasticity is decreased by the Fe addition, a fracture strain of approximately 17% is obtained for Ti-15Nb-25Zr-4Fe, indicating a good plasticity. The heat treatment cannot eliminate the segregation of Nb, but can improve the plasticity and slightly increase the strengths of Ti-15Nb-25-Zr(0, 2, 4)Fe. Moreover, the heat-treated Ti-15Nb-25Zr-8Fe exhibits a high strength of approximately 1780 MPa and fracture strain of approximately 19%. Therefore, good comprehensive mechanical properties, including high strengths, high hardnesses, and good plasticities, can be obtained in Fe-added β-Ti alloys prepared by SPS and subsequent optional short heat treatment.Li Q., Yuan X., Li J., et al. Effects of Fe on microstructures and mechanical properties of Ti-15Nb-25Zr-(0, 2, 4, 8)Fe alloys prepared by spark plasma sintering. Materials Transactions 60, 1763 (2019); https://doi.org/10.2320/matertrans.ME201913

The application of nanomedicine in clinical settings

As nanotechnology develops in the fields of mechanical engineering, electrical engineering, information and communication, and medical care, it has shown great promises. In recent years, medical nanorobots have made significant progress in terms of the selection of materials, fabrication methods, driving force sources, and clinical applications, such as nanomedicine. It involves bypassing biological tissues and delivering drugs directly to lesions and target cells using nanorobots, thus increasing concentration. It has also proved useful for monitoring disease progression, complementary diagnosis, and minimally invasive surgery. Also, we examine the development of nanomedicine and its applications in medicine, focusing on the use of nanomedicine in the treatment of various major diseases, including how they are generalized and how they are modified. The purpose of this review is to provide a summary and discussion of current research for the future development in nanomedicine

Nanotechnology in cervical cancer immunotherapy: Therapeutic vaccines and adoptive cell therapy

Immunotherapy is an emerging method for the treatment of cervical cancer and is more effective than surgery and radiotherapy, especially for recurrent cervical cancer. However, immunotherapy is limited by adverse effects in clinical practice. In recent years, nanotechnology has been widely used for tumor diagnosis, drug delivery, and targeted therapy. In the setting of cervical cancer, nanotechnology can be used to actively or passively target immunotherapeutic agents to tumor sites, thereby enhancing local drug delivery, reducing drug adverse effects, achieving immunomodulation, improving the tumor immune microenvironment, and optimizing treatment efficacy. In this review, we highlight the current status of therapeutic vaccines and adoptive cell therapy in cervical cancer immunotherapy, as well as the application of lipid carriers, polymeric nanoparticles, inorganic nanoparticles, and exosomes in this context

Low springback and low Young’s modulus in Ti-29-Nb-13Ta-4.6Zr alloy modified by Mo addition

Deformation-induced higher Young’s modulus can satisfy the contradictory requirements of Ti alloys for spinal-fixation applications, which demand a high Young’s modulus to reduce springback during operations and a low Young’s modulus to prevent stress shielding effect for patients after surgeries. In this study, TNTZ-(1, 3, 5)Mo are designed by adding Mo and Ti to Ti-29-Nb-13Ta-4.6Zr (TNTZ) in order to maintain low initial Young’s modulus and achieve low springback. All the solutionized alloys show single β phase with increasing the β stability by Mo addition. They show low Young’s moduli less than 65 GPa, similar ultimate tensile strength of 650 MPa and elongation around 20%. The springback of TNTZ-3Mo and TNTZ-5Mo is lower than that of TNTZ and TNTZ-1Mo owing to their more stable β phase. After cold rolling, TNTZ-3Mo shows the largest increasing ratio of 25% in Young’s modulus and the highest ultimate tensile strength owning to the appearance of deformation-induced ω phase. With the low initial Young’s modulus of 59 GPa, TNTZ-3Mo is a potential candidate to make the spinal rods in spinal fixation devices.Li Q., Qi Q., Li J., et al. Low springback and low Young’s modulus in Ti-29-Nb-13Ta-4.6Zr alloy modified by Mo addition. Materials Transactions 60, 1755 (2019); https://doi.org/10.2320/matertrans.ME201912

Characterization and anti-aging activities of polysaccharide from Rana dybowskii Guenther

Introduction:Rana dybowskii Guenther (RDG), as a traditional Chinese medicine, has been shown to have antioxidant effects. However, studies on the anti-aging effect of RDG are still limited.Methods: In this study, we prepared polysaccharides from the skin of RDG (RDGP) by hot water extraction, alcohol precipitation, ion-exchange chromatography and gel chromatography. The proteins were removed using the Sevage method in combination with an enzymatic method. The structural features were analyzed using high-performance gel permeation chromatography, β-elimination reaction and Fourier transform infrared spectra. The anti-aging effect of RDGP was investigated by using D-Gal to establish an aging model in mice, and pathological changes in the hippocampus were observed under a microscope.Results: We obtained the crude polysaccharide DGP from the skin of RDG, with a yield of 61.8%. The free protein was then removed by the Sevage method to obtain DGPI and deproteinated by enzymatic hydrolysis combined with the Sevage method to further remove the bound protein to obtain the high-purity polysaccharide DGPII. Then, DGPIa (1.03 × 105 Da) and DGPIIa (8.42 × 104 Da) were obtained by gel chromatography, monosaccharide composition analysis showed that they were composed of Man, GlcA, GalNAc, Glc, Gal, Fuc with molar ratios of 1: 4.22 : 1.55: 0.18 : 8.05: 0.83 and 0.74 : 1.78: 1: 0.28: 5.37 : 0.36, respectively. The results of the β-elimination reaction indicated the presence of O-glycopeptide bonds in DGPIa. The Morris water maze test indicated that mice treated with DGPIIa exhibited a significantly shorter escape latency and increased time spent in the target quadrant as well as an increase in the number of times they traversed the platform. Pathologic damage to the hippocampus was alleviated in brain tissue stained with hematoxylin-eosin. In addition, DGPIIa enhanced the activities of SOD, CAT, and GSH-Px and inhibited the level of MDA in the serum and brain tissues of aging mice.Discussion: These results suggest that RDGP has potential as a natural antioxidant and provide useful scientific information for anti-aging research

Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis

Transferrin receptor 1 (Tfr1) mediates the endocytosis of diferric transferrin in order to transport iron, and Tfr1 has been suggested to play an important role in hematopoiesis. To study the role of Tfr1 in hematopoiesis, we generated hematopoietic stem cell (HSC) specific Tfr1 knockout mice. We found that Tfr1 conditional knockout mice reached full term but died within one week of birth. Further analyses revealed that Tfr1-deficient HSC had impaired development of all hematopoietic progenitors except thrombocytes and B lymphocytes. In addition, Tfr1-deficient cells had cellular iron deficiency, which blocked the proliferation and differentiation of hematopoietic precursor cells, attenuated the commitment of hematopoietic lineages, and reduced the regeneration potential of HSC. Notably, hemin rescued the colony-forming capacity of Tfr1-deficient HSC, whereas expressing a mutant Tfr1 that lacks the protein’s iron-transporting capacity failed to rescue hematopoiesis. These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells