Long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been reported to play a key role in the progression of diabetic nephropathy (DN). However, the role of lncRNA TUG1 in the regulation of ...diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice. Afterwards, computational prediction programs (TargetScan, miRanda, PicTar and miRGen) was applied to predict the target gene of miRNAs. The complementary binding of miRNA and lncRNA was assessed by luciferase assays. Protein and mRNA expression were detected by western blot and real time quantitate PCR. MiRNA-377 was screened by miRNA microarray and differentially up-regulated in db/db DN mice. PPARγ was predicted to be the target of miR-377 and the prediction was verified by luciferase assays. Expression of miR-377 was up-regulated in mesangial cell treated with high glucose (25 mM), and overexpression of miR-377 inhibited PPARγ expression and promoted PAI-1 and TGF-β1 expression. The expression of TUG1 antagonized the effect of miR-377 on the downregulation of its target PPARγ and inhibited extracellular matrix accumulation, including PAI-1, TGF-β1, fibronectin (FN) and collagen IV (Col IV), induced by high glucose. LncRNA TUG1 acts as an endogenous sponge of miR-377 and downregulates miR-377 expression levels, and thereby relieving the inhibition of its target gene PPARγ and alleviates extracellular matrix accumulation of mesangial cells, which provides a novel insight of diabetic nephropathy pathogenesis.
•MiR-377 is up-regulated in db/db DN mice.•MiR-377 suppresses its target gene PPARγ expression.•LncRNA TUG1 acts as an endogenous sponge of miR-377.•LncRNA TUG1 alleviates extracellular matrix accumulation of mesangial cells.
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional ...Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.
As the major producer and consumer of hydrofluorocarbons (HFCs), China is obligated to phase-down HFCs to mitigate global warming if China ratifies the Kigali Amendment (KA) to the Montreal Protocol. ...Based on historical HFCs consumption in each sector, here we estimated historical HFCs emissions with a bottom-up method, and projected the consumption baseline and schedule for HFCs phase-down in China under the KA and the corresponding potential for emission reduction. Results showed that China's HFCs consumption and emissions in 2017 were 164,000 t (311 Mt CO2-eq) and 108 Mt CO2-eq, respectively. HFCs consumption baseline was projected to be (724 ± 18) Mt CO2-eq in 2024, and China should take measures to phase-down HFCs by 2029, at the latest, to meet the requirements of the KA. HFCs consumption in 2050 under KA would reach the level of 2012–2013. Cumulative reduced consumption was estimated at 10.8 (10.1–11.6) Gt CO2-eq, and cumulative reduced emissions were estimated at 5.38 (4.90–5.64) Gt CO2-eq by 2050.
High glucose (HG)-induced pancreatic β-cell apoptosis may be a major contributor to the progression of diabetes mellitus (DM). NADPH oxidase (NOX2) has been considered a crucial regulator in β-cell ...apoptosis. This study was designed to evaluate the impact of GLP-1 receptor agonist (GLP-1Ra) liraglutide on pancreatic β-cell apoptosis in diabetes and the underlying mechanisms involved.
The diabetic rat models induced by streptozotocin (STZ) and a high fat diet (HFD) received 12 weeks of liraglutide treatment. Hyperglycemic clamp test was carried out to evaluate β-cell function in vivo. Flow cytometry analysis was used to measure apoptosis rates in vitro. DCFH-DA method was used to detected ROS level in vivo and in vitro.
Liraglutide significantly improved islet function and morphology in diabetic rats and decreased cell apoptosis rates. Thr183/Thr185 p-JNK1/2 and NOX2 levels reduced in diabetic rats and HG-induced INS-1 cell following liraglutide treatment. In addition, liraglutide upregulated the phosphorylation of AMPKα (p-AMPKα), which prevented NOX2 activation and alleviated HG-induced β-cell apoptosis.
The p-AMPKα/NOX2/JNK1/2 pathway is essential for liraglutide to attenuate HG-induced β-cell apoptosis, which further proves that GLP-1Ras may become promising therapeutics for diabetes mellitus.
Background：Obstructive sleep apnea syndrome （OSAS） has been shown to generate hypertension and endothelial dysfunction.Retinal vessel is the only vessel that can be observed directly and ...noninvasively;retinal vascular abnormalities can serve as a predictive marker for the occurrence,clinical course,and prognosis of cardiovascular and cerebrovascular diseases.The objective of this study was to identify the effect of OSAS severity on the morphological changes of retinal vessels.Methods：Adult patients complained of snoring were included in this study.The patients＆#39; general information,polysomnography,and fundus photography parameters including central retinal artery equivalent （CRAE）,central retinal vein equivalent （CRVE）,and arteriole-to-venule ratio （AVR） were collected.Patients were divided into four groups according to their apnea-hypopnea index （AHI） results：Group Ⅰ,AHI ≤5/h;Group ll,5/h 〈 AHI ≤30/h;Group Ⅲll,30/h 〈 AHI ≤60/h;and Group Ⅳ,AHI 〉60/h.Results：A total of 133 patients were included in this study with 111 males （83.5%） and 22 females （16.5%）.Mean age was 41.6 ± 9.9 years,and the mean body mass index was 28.1 ± 4.0 kg/m2.AHI ranged between 0 and 130.8/h with a mean of 39.l ± 30.7/h.There were 24,34,35,and 40 patients in Group Ⅰ,Group Ⅱ,Group Ⅲ,and Group Ⅳ,respectively.Significant differences were found for AHI （F =388.368,P 〈 0.001）,minimal pulse oxygen saturation （F-91.902,P 〈 0.001）,and arousal index （F =31.014,P 〈 0.001） among four groups;no significant differences were found for CRAE （F=0.460,P =0.599） and CRVE （F =0.404,P =0.586） among groups;there were significant differences for AVR between Group l and Group Ⅳ （63.6 ± 5.1% vs.67.2 ± 5.5%,P =0.010） Group Ⅱ and Group Ⅳ （64.5 ± 6.0% vs.67.2 ± 5.5%,P =0.030）,and Group ll and Group Ⅳ （64.7 ± 4.1% vs.67.2 ± 5.5%,P=0.043）.A main group-by-AHI effect was found on the AVR：patients with higher AHI showed higher AVR results （r =0.225,P =0.009）.Multivariate logistic regression analysis was used for multi-variable factors.A group-by-age effect was found on the AVR：younger patients showed higher AVR results （β =-0.001,P =0.020）.Conclusions：This study indicated that increased AVR of retinal vessel can be observed in extremely severe OSAS patients.For patients with OSAS,retinal vascular abnormalities may become an early indication for further cardiovascular abnormalities.
With the Kigali Amendment (KA) coming into effect in China, the control of hydrofluorocarbons (HFCs) emissions has become more imperative. The mobile air-conditioning (MAC) sector is one of the ...important HFCs consumer sectors, and therefore studying its feasible mitigation paths and costs is of great significance to China's successful implementation of KA. This study used the bottom-up method with updated emission factors to re-evaluate the emission inventory of HFCs from the MAC sector in China from 2005 to 2020. The average annual growth rate of HFCs consumption in the MAC sector is 9.8%, and HFCs emissions have increased from 5.8 (5.3–6.2) kt in 2005 to 22.2 (20.6–23.8) kt in 2020, with an average annual growth rate of 8.8%. Using the Gompertz model combined with the Weibull function of vehicle survival rate, the ownership and new registrations of internal combustion engine vehicles (ICEVs) and electric vehicles (EVs) in China are predicted. The ownership of ICEVs and EVs is projected to be 310 million and 91 million in 2030, respectively and 2 million and 641 million in 2060, respectively. HFCs emissions in the MAC sector would reach 59.8 (55.3–64.3) kt (80.0–93.0 Mt CO2-eq) in 2060 if without any control measure. To implement the KA, the cumulative of 1.6 Gt CO2-eq emissions would be reduced. Under the other two accelerated mitigation scenarios, the MAC sector's HFCs will reach their emissions peak in 2028 and 2025 and achieve zero emissions in 2050 and 2046, respectively. Under the accelerated mitigation with recovery scenario, the cumulative emissions are only 15.0% of the business as usual (BAU) scenario. Using HFO-1234yf as the substitute, the unit abatement cost of the MAC sector is 27.3–37.4 USD t−1 CO2-eq.
Background：Obstructive sleep apnea/hypopnea syndrome （OSAHS） and laryngopharyngeal reflux （LPR） disease have a high comorbidity rate,but the potential causal relation between the two diseases remains ...unclear.Our objectives were to investigate the esophageal functional changes in OSAHS patients and determine whether OSAHS affects LPR by affecting esophageal functions.Methods：Thirty-six OSAHS patients and 10 healthy controls underwent 24-h double-probed combined esophageal multichannel intraluminal impedance and pH monitoring simultaneously with polysomnography.High-resolution impedance manometry was applied to obtain a detailed evaluation of pharyngeal and esophageal motility.Results：There were 13 OSAHS patients （36.1%） without LPR （OSAHS group） and 23 （63.9%） with both OSAHS and LPR （OSAHS and LPR group）.Significant differences were found in the onset velocity of liquid swallows （OVL,P =0.029） and the percent relaxation of the lower esophageal sphincter （LES） during viscous swallows （P =0.049） between the OSAHS and control groups.The percent relaxation of LES during viscous swallows was found to be negatively correlated with upright distal acid percent time （P =0.016,R =-0.507）,and OVL was found to be negatively correlated with recumbent distal acid percent time （P =0.006,R =-0.557） in the OSAHS and LPR group.Conclusions：OSAHS patients experience esophageal functional changes,and linear correlations were found between the changed esophageal functional parameters and reflux indicators,which might be the reason that LPR showed a high comorbidity with OSAHS and why the severity of the two diseases is correlated.
After the Kigali Amendment (KA) came into effect, HCFC-22 plants are obliged to limit HFC-23 emissions. Therefore, the study of cost-effective mitigation pathways for HFC-23 is important for the ...sustainable implementation of KA in China and other HCFC-22 producing countries. This study constructed an inventory of HFC-23 by-production, emissions, and abatement for HCFC-22 plants in China from 2006 to 2020, and predicted the costs and climate benefits of HFC-23 abatement in China's compliance with the KA between 2021 and 2060. Results showed that HFC-23 emissions from HCFC-22 plants in China contributed about 60% of the growth in global atmospheric mole fraction of HFC-23 observed by Advanced Global Atmospheric Gases Experiment (AGAGE) from 2007 to 2020. Furthermore, China's cumulative HFC-23 abatement was about 109 kt (1613 Mt CO2-eq) from 2006 to 2019, accounting for 53% of total by-production, which allowed the global atmospheric mole fraction and radiative forcing of HFC-23 in 2020 to avoid an uplift of 9.2 × 10−9 and 1.7 mW m−2, respectively, contributing to climate change mitigation. Under the baseline of the Kigali Amendment, less emission (LE), and resource utilization (RU) scenarios, the cumulative HFC-23 abatement from 2021 to 2060 would be 683 ± 29 kt (10,107 ± 431 Mt CO2-eq), 694 ± 29 kt (10,277 ± 427 Mt CO2-eq), and 702 ± 29 kt (10,385 ± 426 Mt CO2-eq), respectively. The cumulative net abatement costs for the KA, LE, and RU scenarios would be (5.0 ± 0.2) billion, (2.9 ± 0.2) billion, and (−2.7 ± 0.2) billion CNY (2021 prices), respectively. In the future, applying resource utilization technology to reduce HFC-23 emissions can achieve both climate and economic benefits.
Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived ...factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the saxagliptin-treated diabetic rats, subsequently the key WNT-signaling regulators, β-catenin, and AKT were activated. However, the effect of saxagliptin inducing β-cell proliferation was attenuated when we silenced the SDF-1α receptor (CXCR4) with RNAi in INS cell lines. Collectively, our data indicate that SDF-1α mediates the protective effect of saxagliptin on β-cell proliferation, suggesting that DPP-4 inhibitors have the potential role on delaying β-cell failure and SDF-1α could be a therapeutic target of β-cell regeneration.
Aim： To investigate the effects of liraglutide, a glucagon-like peptide-1 （GLP-1） receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. ...Methods： A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with Iiraglutide once dally for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Statistical analyses were performed using SPSS software package version 3.1.5 for Windows. Results： Liraglutide treatment caused significant reduction of the mean body weight （from 86.61±14.09 to 79.10±13.55 kg） and waist circumference （from 101.81±13.96 to 94.29±14.17 cm）, resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss above 10% in 34.06% patients, who had significant lower plasma creatinine levels. Baseline waist circumference, BMI and HOMA-IR were independently correlated with the body weight loss. Furthermore, liraglutide treatment significantly decreased HbAlc levels （from 8.66%±2.17% to 6.92%±0.95%） with HbA1c〈7.0% in 35,37% patients, who had a significantly lower baseline level of HbAlc, but higher baseline levels of C peptide and glucagon. Moreover, liraglutide treatment resulted in greater body weight loss in patients with a long duration of diabetes, and better glycemic control in patients with a short duration of diabetes. Conclusion： Liraglutide significantly reduces body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Patients with apparent visceral obesity, insulin resistance and a long duration of diabetes may have greater body weight loss whereas patients with high insulin-secreting ability, hyperglucagonemia, and short-duration diabetes may obtain better glycemic contrc with liraglutide.
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