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

Eriodictyol attenuates spinal cord injury by activating Nrf2/HO-1 pathway and inhibiting NF-κB pathway

Purpose: To investigate the effect of eriodictyol on spinal cord injury (SCI) and its underlying mechanism of action.Methods: Thirty Sprague-Dawley rats were assigned to sham, SCI, and eriodictyol-treated groups (SCI + Eri; 10, 20, and 50 mg/kg). Moderate spinal cord contusion injury was induced to model SCI. Locomotor recovery was assessed based on Basso, Beattie, and Bresnahan (BBB) score. Pain wasevaluated by paw withdrawal threshold (PWT) and latency (PWL), and spinal cord water content was measured. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) expression were determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Immunoassay was used to determine malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels while Western blotting was employed to evaluate nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and phosphorylated NF-κB (p-NF-κB) levels.Results: Eriodictyol elevated BBB score, PWT, and PWL in SCI rats but reduced spinal cord water content (p < 0.05). Eriodictyol treatment down-regulated TNF-α, IL-1β, IL-6, and MDA, whereas SOD, GSH, and GSH-PX levels were elevated (p < 0.05). Eriodictyol administration increased Nrf2 and HO-1 levels but reduced p-NF-κB/NF-κB.Conclusion: This study provides a potential therapy to promote long-term functional recovery following SCI. Keywords: Spinal cord injury, Eriodictyol, Nrf2/HO-1 pathway, NF-κB signaling pathway, Polymerase chain reaction, Basso, Beattie and Bresnahan scor

Leczenie oksytocyną zapobiega stłuszczeniu szpiku kostnego obserwowanemu u królików z cukrzycą wywołaną alloksanem — badanie przy użyciu protonowej spektroskopii rezonansu magnetycznego

Introduction: Oxytocin might be used therapeutically as an ally to rescue osteopathy resulting from diabetes. However, the in vivo effects of oxytocin on marrow adipogenesis in diabetes remain unknown. In this longitudinal study, we aimed to investigate the protective ef­fects of oxytocin on diabetes-induced marrow adiposity in rabbits using proton MR spectroscopy. Material and methods: Forty-five female New Zealand rabbits were randomly divided into controls, diabetes, and diabetes treated with oxytocin (ip, 0.78 mg/kg) for six months. Marrow fat fraction (FF) was determined by proton MR spectroscopy at baseline, and at three and six months. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum biomarkers, glycolipid metabolism, and histological analysis of marrow adipocytes were determined. Results: Oxytocin treatment had positive metabolic effects in diabetic rabbits, which was based on the changes in glucose metabolism, insulin sensitivity, and lipid profiles. The diabetic rabbits demonstrated dramatic marrow adiposity in a time-dependent manner; at three and six months the FF percentage changes from baseline were 10.1% and 25.8%, respectively (all P < 0.001). Moreover, oxytocin treatment significantly reversed FF values and quantitative parameters of marrow adipocyte in diabetic rabbits to levels of naive control rabbits. Oxytocin improved bone formation marker in diabetic rabbits compared to the saline group. Also, treatment of diabetic rabbits with oxytocin significantly mitigated bone deterioration when compared with the saline-treated diabetic group (all P < 0.05). Conclusions: Oxytocin appears to alleviate harmful effects of hyperglycaemia on marrow adiposity. Proton MR spectroscopy may be a valuable tool, providing complementary information on efficacy assessments.Wstęp: Oksytocyna może być stosowana terapeutycznie w osteopatii wynikającej z cukrzycy, jednakże jej wpływ in vivo na stłuszczenie szpiku kostnego w przebiegu cukrzycy pozostaje niezbadany. Niniejsze badanie przekrojowe ma na celu zbadać ochronne działanie oksy­tocyny na wywołane cukrzycą stłuszczenie szpiku kostnego u królików przy użyciu protonowej spektroskopii rezonansu magnetycznego. Materiał i metody: Czterdzieści pięć samic królików nowozelandzkich podzielono losowo na grupę kontrolną, grupę z cukrzycą oraz grupę z cukrzycą leczoną oksytocyną (0.78 mg/kg, i.p.) przez sześć miesięcy. Frakcja tłuszczu (ang. fat fraction; FF) szpiku kostnego została określona za pomocą protonowej spektroskopii rezonansu magnetycznego na początku badania oraz po trzech i sześciu miesiącach. Gęstość mineralną kości zmierzono za pomocą absorpcjometrii promieniowania rentgenowskiego o podwójnej energii. Określono również biomarkery surowicy krwi, metabolizm glikolipidów oraz sporządzono analizę histologiczną adipocytów szpiku kostnego. Wyniki: Leczenie oksytocyną przyniosło pozytywne efekty metaboliczne u królików z cukrzycą, co stwierdzono na podstawie zmian w me­tabolizmie glukozy, wrażliwości na insulinę oraz profili lipidowych. Zauważono drastyczny wzrost stłuszczenia szpiku kostnego u królików z cukrzycą w sposób zależny od czasu; po trzech i sześciu miesiącach, procentowe zmiany frakcji tłuszczu w stosunku do wartości wyjściowej wynosiły odpowiednio 10,1% i 25,8% (wszystkie P &lt; 0.001). Co więcej, leczenie oksytocyną znacząco odwracało wartości frakcji tłuszczu oraz ilościowe parametry adipocytów szpiku kostnego u królików z cukrzycą do poziomu królików z grupy kontrolnej. Oksytocyna poprawiała marker tworzenia kości u królików z cukrzycą w porównaniu do grupy, której podawano sól fizjologiczną. Ponadto, leczenie oksytocyną królików z cukrzycą znacząco łagodziło niszczenie kości w porównaniu do grupy z cukrzycą, której podawano sól fizjologiczną (wszystkie P &lt; 0.05). Wnioski: Oksytocyna wydaje się zmniejszać szkodliwy wpływ hiperglikemii na stłuszczenie szpiku kostnego. Protonowa spektroskopia rezonansu magnetycznego może być cennym narzędziem, dostarczającym uzupełniających informacji na temat oceny skuteczności leczenia

A chromosome conformation capture ordered sequence of the barley genome

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Occurrence, Distribution, and Risk Assessment of Antibiotics in the Aquatic Environment of the Karst Plateau Wetland of Yangtze River Basin, Southwestern China

In this study, the occurrence, distribution, and ecological risk of 40 commonly used antibiotics, including 15 sulfonamides (SAs), 9 fluoroquinolones (FQs), 7 macrolides (MCs), 3 tetracyclines (TCs), 2 chloramphenicols (CAPs), and 4 other categories, in the aquatic environment of the karst plateau wetland Caohai of the Yangtze River basin in southwestern China are reported. In total, 27 antibiotics were detected, with the detection rate ranging from 5% to 100%. The total concentration at each site ranged from 21.8 ng/L to 954 ng/L, with the average concentration being 189 ng/L. FQs and MCs were the most predominant categories, contributing 29.3% and 25.0% of the total antibiotic burden. The five most commonly detected antibiotics were ciprofloxacin (CIP), oxytetracycline (OTC), acetyl sulfamethoxazole (ASMZ), norfloxacin (NOR), and florfenicol (FF). The spatial distribution of the total concentration at each site demonstrated a decreasing trend from the southeastern area upstream adjoining the main counties to the northwestern area downstream, indicating that human activities have a great impact. Meanwhile, the natural attenuation rates of different types of antibiotics in the direction of flow ranged from 17.6% to 100%, which implied the natural purification potential of the wetland for antibiotics. The cluster analysis results indicated that domestic sewage and wastewater from agriculture and animal husbandry were the main sources of contamination in the surrounding wetland. Risk quotients (RQs) assessment showed that most of the individuals were at low to medium risk and that the adverse risks posed by mixtures of antibiotics were higher than those posed by the individual antibiotics

Self-tunable ultrathin carbon nanocups as the electrode material of sodium- ion batteries with unprecedented capacity and stability

Structural instability and limited operational efficiency of sodium-ion battery (SIB) anodes, compared lithium-ion battery (LIB) anodes, are main hurdles for their large-scale applications that can be tackled using self-tunable electrode materials. Here, we created and utilized ultrathin partially-crystalline carbon nanocups (CNCs) that have the ability to self-tune their structure, contain highly tangled walls and present open framework for enhanced energy densities for SIBs and the outcomes are benchmarked with LIBs. The tangled wall structure offers enhanced spacings for ionic storage and the open framework supports enhanced mass transport, while partial-crystallinity of CNCs provides high conductivity and stabilizes the structure for long cycle life. The CNCs delivered high capacities up to 468 mAh/g for SIBs at 25 mA/g and 953 mAh/g for LIBs at 50 mA/g after 100 cycles, respectively, while bore excellent stability by delivering highly stable performance exceeding 1000 cycles for SIBs at 1.5 A/g and 5000 cycles for LIBs at 7.5 A/g (20 C) with only a loss of 0.013 mAh/g per cycle. Moreover, when tested in lower voltage ranges, the CNCs delivered unprecedented capacity of 368 mAh/g (0.01-2.0 V) for SIBs and 671 mAh/g (0.01-2.0 V) and 449 mAh/g (0.01-1.5 V) for LIBs at 25 and 50 mA/g, respectively, which indicate the usability of the CNCs in full-cells. The post-electrochemical characterizations revealed that the developed CNCs self-modified their interlayer spacings (average spacing increased to 0.44 nm from 0.42 nm) during charge-discharge to create additional voids for increased ionic storage and stable performance, especially for Na+, while maintaining their overall morphology, composition and structure. The structural design presented here will provide new pathways of tailoring carbonaceous nanostructures for future high-performance energy storage devices