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

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

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

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

Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19

Summary Background COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required. Methods We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots. Findings The final model included age, lymphocyte count, lactate dehydrogenase and SpO 2 as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data. Interpretation COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate. Funding This study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK. Research in context Evidence before this study Since the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date. Added value of this study In our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO 2 remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings. Implication of all the available evidence After further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome