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Wogonoside (WG) is a flavonoid chemical component extracted from Scutellaria baicalensis, which exerts therapeutic effects on liver diseases. Ferroptosis, a novel form of programmed cell death, regulates diverse physiological/pathological processes. In this study, we attempted to investigate a novel mechanism by which WG mitigates liver fibrosis by inducing ferroptosis in hepatic stellate cells (HSCs). A CCl

The stability of soil mass near the dam bank in the Three Gorges Reservoir is closely related to the periodic variation in the reservoir water level. In order to study the influence of water level variation on soil mass, the soil mass in the water level fluctuation zone of the Wildcat landslide was taken as the research object, and the mechanism of soil mass deterioration in this area was revealed by comparing the strength and mineral structure characteristics of soil mass at different elevations by means of macro- and meso-microscopic analysis. The results show the following: (1) With the increase in sampling elevation, the natural water content of the soil decreases, and the dry density of the soil is a minimum when the elevation is 155 m and at a maximum when the elevation is 175 m. (2) The soil mass in the water dissipation zone of the Wildcat landslide can be divided into three areas: When the elevation is 145–155 m, the fractal dimension increases, the soil fragmentation increases, the cohesion decreases, and the soil deterioration increases. When the elevation is 155–175 m, the fractal dimension decreases, the soil fragmentation decreases, the cohesion increases, and the soil deterioration weakens. When the elevation is greater than 175 m, there is no soil deterioration. (3) X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) were used to test the soil’s mineral composition and pore size at different elevations. It was found that the main reason for the severe deterioration of macro-strength parameters of the soil at the elevation of 155 m was that the proportion of clay minerals and quartz was at the lowest, and the proportion of medium pores and large pores was at the highest. (4) Through the combination of macro and mesoscopic testing and analysis, it was found that the rise and fall of the reservoir water level will lead to the strong chemical action of the skeleton and cemented mineral dissolution in the soil degradation-enhanced area, as well as the physical action of soil particles, resulting in the formation of more medium pores and large pores in the soil and eventually the formation of seepage channels.

DNA amplification is one of the most valuable tools for the clinical diagnosis of nucleic acid-related diseases, but current techniques for DNA amplification are based on intermolecular polymerization reactions, resulting in the risk of errors in the intermolecular reaction pattern. In this article, we introduce the concept of intramolecular polymerization and isomerization cyclic amplification (PICA), which extends a short DNA strand to a long strand containing periodic repeats of a sequence through cyclic alternating polymerization and isomerization. To the best of our knowledge, this is the first time that a real ssDNA self-extension method without any additional auxiliary oligonucleotides has been reported. By interfacing PICA with external molecular elements, it can be programmed to respond to different targets. Herein, we designed two distinct types of amplified nucleic acid detection platforms that can be implemented with PICA, including cyclic reverse transcription (CRT) and cyclic replication (CR). We experimentally demonstrate the mechanisms of CRT-PICA and CR-PICA using mammalian miRNA and virus DNA. The results showed that this proposed detection platform has excellent sensitivity, selectivity, and reliability. The detection level could reach the aM level, that is, several copies of target molecules can be detected if a small volume is taken into account., DNA amplification is one of the most valuable tools for the clinical diagnosis of nucleic acid-related diseases, but current techniques for DNA amplification are based on intermolecular polymerization reactions, resulting in the risk of errors in the intermolecular reaction pattern.

Diabetic hepatic fibrosis (DHF) is a progressive liver disease and a chronic complication of diabetes mellitus. The main cause of DHF is the activation of quiescent hepatic stellate cells (HSCs) by high glucose stimulation. Dopamine receptor D2 (DRD2)-mediated dopamine signalling can be involved in the regulation of diabetic liver disease, but the exact role of DRD2 in DHF is still poorly understood. This study aimed to investigate the protective effect of DRD2 inhibition on diabetic liver fibrosis and the potential mechanism. We established both streptozotocin (STZ)-induced type 1 diabetes (T1D, fed for 20 weeks) rat model and high glucose (HG, 40 mmol/L)-stimulated HSCs model. The results from both the rats with STZ and the HSCs treated with HG showed increased expression of DRD2, NOX-5, inflammation-related proteins (IL-6 and TNFα) and fibrosis-related proteins (TGF-β1, CO-Ⅰ/Ⅲ/ IV, MMP-2/9 and fibronectin). In vivo, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (T-AOC) levels were significantly increased, and hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy revealed liver lesions and hepatocyte injury. In addition, HG-treated HSCs exhibited altered oxidative stress - related indexes, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS), changed and abnormally proliferated in vitro. TGF-β1, the phosphorylated Smad2, nuclear NFκB-p65, phosphorylated NFκB-p65 and phosphorylated IκBα were also increased. Interestingly, haloperidol (DRD2 inhibitor) and n-acetyl-L-cysteine (NAC, an active oxygen scavenger) reduced the above-mentioned changes. In conclusion, DRD2 inhibition can reduce diabetic HSCs oxidative damage and fibrotic proliferation partly via the TGF-β1/Smads and NFκB pathways.

We designed a soft Cu-based brazing filler (60Cu–40Ag in wt.%) and investigated its wettability and brazeability with 3 mol% yttria-stabilized zirconia (3YSZ) under direct current (DC) application. Increasing the current intensity dramatically accelerated the spreading rate and decreased the final contact angle. When the DC reached 60 mA, the contact angle decreased from 140° to 50° within 50 s and finally stabilized at 26° in approximately 300 s. The change in the stoichiometry of the 3YSZ substrate and the adsorption of Zr at the triple line were presumably responsible for the electrochemically induced wetting improvement. Furthermore, robust joining of 3YSZ to 304 stainless steel (304 SS) with a shear strength of 215 ± 9 MPa was achieved in only 300 s by applying a DC of 30 mA using this 60Cu–40Ag filler. The AgCu4Zr formed at the 60Cu–40Ag/3YSZ interface was critical for the robust joining. This work provides a novel route for obtaining robust zirconia–metal joints.

The aim of this research was to probe the potential application of nano-titanium dioxide (TiO2)/basic magnesium hypochlorite (BMH)-containing linear low-density polyethylene (LLDPE) composite film in grape fresh-keeping. Mechanical properties, transparency, barrier performance and antibacterial activity of the nano-composite membrane were measured, and results showed that the antibacterial zone diameter of TiO2/BMH on pathogen-Aspergillus niger was 31.4 mm, with mixing ratio of BMH/TiO2 to 2:1. It was clearly shown that the synthesized nano-composite films decreased mechanical properties and transparency of the membrane, and also had a significant impact on sensory score, mass loss rate, decay rate, ascorbic acid (Vc) content and titratable acid content compared with LLDPE films. Moreover, the results revealed that the LLDPE antibacterial film can be effectively used for storing grapes, preserving the flavor of grapes and had an obviously effect in prolonging grapes’ shelf life.

Myocardial fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Spermine (SPM), a product of polyamine metabolism, plays an important role in many cardiac diseases including hypertrophy, ischemia, and infarction, but its role in diabetic myocardial fibrosis has not been clarified. This study aimed to investigate the role of polyamine metabolism, specifically SPM, in diabetic myocardial fibrosis and to explore the related mechanisms. We used intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in Wistar rats and high glucose (HG, 40 mM) stimulated cardiac fibroblasts (CFs) to established a type 1 diabetes (T1D) model in vivo and in vitro, which were pretreated with exogenous SPM (5 mg/kg per day and 5 μM). The results showed that hyperglycemia induced the expression of the key polyamine synthesis enzyme ornithine decarboxylase (ODC) decreased and the key catabolic enzyme spermidine/spermine N1 -acetyltransferase (SSAT) increased compared with those in the control group. The body weight, blood insulin level, and cardiac ejection function were decreased, while blood glucose, heart weight, the ratio of heart weight to body weight, myocardial interstitial collagen deposition, and endoplasmic reticulum stress (ERS)-related protein (glucose-regulated protein-78, glucose-regulated protein-94, activating transcription factor-4, and C/EBP homology protein) expression in the T1D group were all significantly increased. HG also caused an increased expression of Wnt3, β-catenin (in cytoplasm and nucleus), while Axin2 and phosphorylated β-catenin decreased. Exogenous SPM improved the above changes caused by polyamine metabolic disorders. In conclusion, polyamine metabolism disorder occurs in the myocardial tissue of diabetic rats, causing myocardial fibrosis and ERS. Exogenous SPM plays a myocardial protective role via inhibiting of ERS and the canonical Wnt/β-catenin signaling pathway.

Background. Diabetic cardiomyopathy (DbCM) is the main complication and the cause of high mortality of diabetes. Exploring the transcriptomics and proteomics of DbCM is of great significance for understanding the biology of the disease and for guiding new therapeutic targets for the potential therapeutic effect of spermine (SPM). Methods and Results. By using a mouse DbCM model, we analyzed the overall transcriptome and proteome of the myocardium, before/after treatment with SPM. The general state and cardiac structure and function changes of each group were also compared. Diabetes induced an increased blood glucose and serum triglyceride content, a decreased body weight, serum insulin level, and cardiac function-related indexes, accompanied by disrupted myocardial tissue morphology and ultrastructure damage. Using RNA sequencing (RNA-seq), we identified thousands of differentially expressed genes (DEGs) in DbCM with or without SPM treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the DEGs were significantly enriched in lipid metabolism and amino acid metabolism pathways. Specifically, quantitative real-time PCR (qRT-PCR) confirmed that SPM protected DbCM by reversing the expressions of lipid metabolism and amino acid metabolism-related genes, including Alox15, Gm13033, pla2g12a, Ptges, Pnpla2, and Acot1. To further reveal the pathogenesis of DbCM, we used proteome-based data-independent acquisition (DIA) and identified 139 differentially expressed proteins (DEPs) with 67 being upregulated and 72 being downregulated in DbCM. Venn intersection analysis showed 37 coexpressed genes and proteins in DbCM, including 29 upregulation and 8 downregulation in DbCM. In the protein-protein interaction (PPI) network constructed by the STRING database, the metabolism-related coexpressed genes and proteins, such as Acot2, Ephx2, Cyp1a1, Comt, Acox1, Hadhb, Hmgcs2, Acot1, Inmt, and Cat, can interact with the identified DEGs and DEPs. Conclusion. The biomarkers and canonical pathways identified in this study may hold the key to understand the mechanisms of DbCM pathobiology and provide new targets for the therapeutic effect of SPM against DbCM by targeting lipid and amino acid metabolism pathways.

Background. It is well-known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose- (HG-, 30 mM) treated VSMCs in vitro. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR-182-5p, and tribble 3 (TRIB3). Then, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR-182-5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit-8 assay, 5-ethynyl-2 ′ -deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results. In HG-induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR-182-5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR-182-5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR-182-5p, by directly sponging miR-182-5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR-182-5p inhibition. Conclusion. This study reveals that hsa_circRNA_0008028 can act as a sponge of miR-182-5p and promote HG-induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.

Hydrogen sulfide (H

Objectives Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti‐fibrotic effect of sorafenib. Materials and Methods The effects of sorafenib on HSC ferroptosis and ECM expression were assessed in mouse model of liver fibrosis induced by CCl4. In vitro, Fer‐1 and DFO were used to block ferroptosis and then explored the anti‐fibrotic effect of sorafenib by detecting α‐SMA, COL1α1 and fibronectin proteins. Finally, HIF‐1α siRNA, plasmid and stabilizers were applied to assess related signalling pathway. Results Sorafenib attenuated liver injury and ECM accumulation in CCl4‐induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins. In sorafenib‐treated HSC‐T6 cells, ferroptotic events (depletion of SLC7A11, GPX4 and GSH; accumulation iron, ROS and MDA) were discovered. Intriguingly, these ferroptotic events were not appeared in hepatocytes or macrophages. Sorafenib‐elicited HSC ferroptosis and ECM reduction were abrogated by Fer‐1 and DFO. Additionally, both HIF‐1α and SLC7A11 proteins were reduced in sorafenib‐treated HSC‐T6 cells. SLC7A11 was positively regulated by HIF‐1α, inactivation of HIF‐1α/SLC7A11 pathway was required for sorafenib‐induced HSC ferroptosis, and elevation of HIF‐1α could inhibit ferroptosis, ultimately limited the anti‐fibrotic effect. Conclusions Sorafenib triggers HSC ferroptosis via HIF‐1α/SLC7A11 signalling, which in turn attenuates liver injury and fibrosis., Sorafenib triggers hepatic stellate cell ferroptosis by inhibiting the HIF‐1α/SLC7A11 pathway to attenuate liver fibrosis. Treatment with sorafenib induces a decrease of HIF‐1α, which in turn reduces SLC7A11 expression in HSCs. Then leads to GPX4, GSH depletion and ROS excess, and ultimately induces HSC ferroptosis and ECM reduction.

Background: To investigate the protective effect and possible mechanism of atorvastatin pretreatment on renal function after cardiopulmonary bypass (CPB) in rats. Methods: Twenty-four adult male Sprague-Dawley (SD) rats randomly were divided into three groups: Sham operation group, CPB group, and administration group (N = 8 in each group). The caudal artery and right jugular vein were used to establish the CPB circuit for the CPB and administration groups. Drugs were administered by oral gavage one week before the operation. All rats were executed for succeeding experiments 72h after the operation. Plasma levels of creatinine (Cre) and IL-8 at different time points and levels of TNF-α and MPO in renal tissue were detected by ELISA. Renal pathological changes were observed by HE staining. PPAR-γ expression was determined by immunohistochemistry and western blot. Results: All rats survived the whole process without incident. Renal function of rats undergoing CPB was impaired to varying degrees based on the plasma Cre concentration, and atorvastatin pretreatment alleviated this effect. The concentrations of six inflammatory cytokines (IL-1β, IL-6,IL-8, IFN-γ,TNF-α, and MPO) were significantly elevated after CPB procedure, while atorvastatin pretreatment ameliorated the inflammatory condition caused by CPB. Further analysis showed that in both HK-2 cells and renal tissues, atorvastatin promoted the expression of PPAR-γ. Conclusion: Atorvastatin pretreatment exerted protective effect on CPB-associated kidney injury and inflammation in rats. The activation of PPAR-γ may contribute to the protective effect of Atorvastatin.

Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the patients with diabetes. The calcium sensing receptor (CaSR) is a G protein-coupled receptor, which is involved in maintaining calcium homeostasis, regulating cell proliferation and apoptosis, and so on. In our previous study, we found that CaSR expression, intracellular calcium levels and cardiac function were all significantly decreased in DCM rats; however, the exact mechanism are not clear yet. The present study revealed the protective role of CaSR in myocardial energy metabolism disorder induced by high glucose (HG) as well as the underlying mechanism. Here, we demonstrated that HG decreased the expression of CaSR, mitochondrial fusion proteins (Mfn1, Mfn2), cell gap junction related proteins (Cx43, β-catenin, N-cadherin), and intracellular ATP concentration. In contrast, HG increased extracellular ATP concentration, the expression of gp78, mitochondrial fission proteins (Fis1, Drp1), and the ubiquitination levels of Mfn1, Mfn2 and Cx43. Moreover, CaSR agonist and gp78-siRNA significantly reduced the above changes. Taken together, these results suggest that HG induces myocardial energy metabolism disorder via decrease of CaSR expression, and activation of gp78-ubiquitin proteasome system. In turn, these effects disrupt the structure and function of the mitochondria and the cell gap junction, result in the reduced ATP synthesis and the increased ATP leakage. Stimulation of CaSR significantly attenuates HG-induced abnormal myocardial energy metabolism, suggesting CaSR would be a promising potential therapeutic target for DCM.

In order to study the effect of electromagnetic compound treatment on the mechanical property, cutting performance and microstructure of cemented carbide, the samples were treated by a self-made electromagnetic compound treatment device with different magnetic field strength (H=1, 1.25 and 1.5 T). The electromagnetic compound treatment method was proposed to couple pulsed magnetic field and pulsed current. The results show that after the pulsed magnetic field treatment, the values of the transverse rupture strength of the samples were respectively reduced by 21%, 20.6% and 20.1%; the cutting performance was decreased by about 4.5%, which means the tool life was decreased. After the electromagnetic compound treatment, the values of the transverse rupture strength of the rectangular samples were respectively increased by 8%, 8.6% and 9.5%, and the tool life was increased by 4.2%, 7% and 10.3%. After the electromagnetic compound treatment, the pulse current provided the driving force for dislocation motion. A strong pulse current driving force is more likely to make the dislocation multiply and slip. A high density dislocation cell is formed within the material, so the mechanical properties were significantly increased.

Background and Objectives Calcium-sensing receptor (CaSR) is known to regulate hypoxia-induced pulmonary hypertension (HPH) and vascular remodeling via the phenotypic modulation of pulmonary arterial smooth muscle cells (PASMCs) in small pulmonary arteries. Moreover, autophagy is an essential modulator of VSMC phenotype. But it is not clear whether CaSR can regulate autophagy involving the phenotypic modulation under hypoxia. Methods The viability of human PASMCs was detected by cell cycle and BrdU. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot. Results Our results showed that hypoxia-induced autophagy was considerable at 24 h. The addition of NPS2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways. Conclusions Our study demonstrates that treatment of NPS2390 was conducive to inhibit the proliferation and reverse phenotypic modulation of PASMCs by regulating autophagy levels.

The effects of current polarity, temperature and current intensity on the wettability of 3 mol% yttria-partially stabilized zirconia (3Y-PSZ) by molten 72Ag–28Cu were investigated using a direct current (DC)-coupled sessile drop method. The wettability was significantly improved with the assistance of a DC, especially when 3Y-PSZ was connected to anode. Noticeably, the contact angle rapidly decreased from 143° to smaller than 20° when the current intensity was larger than +10 mA. The wettability also showed abnormal dependence on temperature, presumably due to the competition between nucleation and growth of the m(AgCu4Zr) phase at the interface. The mechanisms for the significant improvement in the wettability under the DC application were ascribed to the formation of substoichiometric ZrO2-δ, the release and adsorption of metallic Zr, and the formation of wettable m(AgCu4Zr) phase at the interface. The DC-assisted wetting provides a new strategy for the rapid and robust joining of 3Y-PSZ to metals.

Hydrogen sulfide (H2S) reduces ischemia/reperfusion (I/R) injury and apoptosis and restores the cardioprotective effects of ischemic post-conditioning (PC) in aged cardiomyocytes by inhibiting oxidative stress and endoplasmic reticulum stress and increasing autophagy. However, the mechanism is unclear. In the present study, we observed a loss of PC-mediated cardioprotection of aged cardiomyocytes. NaHS (a H2S donor) exerted significant protective effects against H/R-induced cell damage, apoptosis, production of cleaved caspase-3 and caspase-9, and release of cytochrome c. NaHS also reversed the H/R-induced reduction in cell viability and increased HB-EGF expression, cellular HB-EGF content, and EGFR phosphorylation. Additionally, NaHS increased expression of Bcl-2, c-myc, c-fos and c-jun, and the phosphorylation of ERK1/2, PI3K, Akt and GSK-3β. PC alone did not provide protection to H/R-treated aged cardiomyocytes, but it was significantly restored by supplementation of NaHS. The beneficial effects of NaHS during PC were inhibited by EGFR knockdown, AG1478 (EGFR inhibitor), PD98059 (ERK1/2 inhibitor) or LY294002 (PI3K inhibitor). These results suggest that exogenous H2S restores PC-mediated cardioprotection by up-regulating HB-EGF/EGFR signaling, which activates the ERK1/2-c-myc (and fos and c-jun) and PI3K-Akt- GSK-3β pathways in the aged cardiomyocytes.

BackgroundAcute ischemic stroke (AIS) leads to a substantial burden of disease among the elderly. There may be a delay in or a poor outcome of endovascular treatment (EVT) among AIS patients with large-vessel occlusion (LVO) during off-hours. By using a prospective, nationwide registry, we compared the workflow intervals and radiological/clinical outcomes between patients with acute LVO treated with EVT presenting during off- and on-hours.MethodsWe analyzed prospectively collected Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) data. Patients presenting during off-hours were defined as those presenting to the emergency department from Monday to Friday between the hours of 17:30 and 08:00, on weekends (from 17:30 on Friday to 08:00 on Monday), and on national holidays. We used logistic regression models with adjustment for potential confounders to determine independent associations between the time of presentation and outcomes.ResultsAmong 1788 patients, 1079 (60.3%) presented during off-hours. The median onset-to-door time and onset-to-reperfusion time were significantly longer during off-hours than on-hours (165 vs 125 minutes, P=0.002 and 410 vs 392 minutes, P=0.027). However, there were no significant differences between patients presenting during off- and on-hours in any radiological/clinical outcomes (mRS score: 3 vs 3 points, P=0.204; mortality: 15.9% vs 14.3%, P=0.172; successful reperfusion: 88.5% vs 87.2%, P=0.579; sICH: 7.2% vs 8.4%, P=0.492).ConclusionsOff-hours presentation in the nationwide real-world registry was associated with a delay in the visit and reperfusion time of EVT in patients with AIS. However, this delay did not lead to worse radiological/clinical outcomes.RegistratonURL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Background This study investigated the effects of the long non-coding (lnc) RNA MT1DP on the apoptosis of nucleus pulposus (NP) cells. The interactions between MT1DP and the microRNA miR-365, and its effects on the anti-oxidant activity of nuclear factor erythroid 2-related factor 2 (NRF-2) were investigated in lumbar disc herniation (LDH). Methods Human degenerative intervertebral disc NP tissues were obtained from 10 patients with LDH who underwent lumbar spine surgery. Normal intervertebral disc NP tissues were obtained from 10 patients with lumbar vertebrae fractures and used as negative controls (NCs). Results The gene expressions of MT1DP and miR-365 in human degenerative disc NP tissues and nucleus pulposus cells (NPCs) were significantly increased, while the level of NRF-2 was significantly decreased. Overexpression of MT1DP and miR-365 (MT1DP + miR-365) and inhibition of NRF-2 suppressed NP cell viability and induced apoptosis. MT1DP + miR-365 caused inflammation in NP cells by damaging the mitochondrial membrane. The combination of lnc-MT1DP and miR-365 reduced cell mitochondrial function and led to a decrease in the ability of cells to elimination reactive oxygen species (ROS). Conclusions The combination of lnc-MT1DP and miR-365 damaged the cell mitochondrial membrane, reduced mitochondrial function and the ability to eliminate ROS, increased cell apoptosis, and caused LDH.

Diabetic nephropathy (DN) is the primary cause of end‑stage renal disease, which is closely associated with dysfunction of the podocytes, the main component of the glomerular filtration membrane; however, the exact underlying mechanism is unknown. Polyamines, including spermine, spermidine and putrescine, have antioxidant and anti‑aging properties that are involved in the progression of numerous diseases, but their role in DN has not yet been reported. The present study aimed to explore the role of polyamines in DN, particularly in podocyte injury, and to reveal the molecular mechanism underlying the protective effect of exogenous spermine. Streptozotocin intraperitoneal injection‑induced type 1 diabetic (T1D) rat models and high glucose (HG)‑stimulated podocyte injury models were established. It was found that in T1D rat kidneys and HG‑induced podocytes, ornithine decarboxylase (a key enzyme for polyamine synthesis) was downregulated, while spermidine/spermine N1‑acetyltransferase (a key enzyme for polyamines degradation) was upregulated, which suggested that reduction of the polyamine metabolic pool particularly decreased spermine content, is a major factor in DN progression. In addition, hyperglycemia can induce an increased rat kidney weight ratio, serum creatinine, urea, urinary albumin excretion and glomerular cell matrix levels, and promote mesangial thickening and loss or fusion of podocytes. The expression levels of podocyte marker proteins (nephrin, CD2‑associated protein and podocin) and autophagy‑related proteins [autophagy protein 5, microtube‑associated proteins 1A/1B light chain 3 (LC3)II/LC3I, Beclin 1 and phosphorylated (p)‑AMPK] were downregulated, while cleaved caspase‑3, P62 and p‑mTOR were increased. These changes could be improved by pretreatment with exogenous spermine or rapamycin (autophagic agonist). In conclusion, spermine may have the potential to prevent diabetic kidney injury in rats by promoting autophagy via regulating the AMPK/mTOR signaling pathway.