Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. ...However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN.
We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β
-microglobulin (β
-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress.
11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to - 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to - 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = - 2.38 to - 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to - 0.33), β
-MG (P < 0.001,SMD = - 2.59, 95%CI = -3.78 to - 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to - 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = - 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to - 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to - 0.34).
α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.
Creating pores in suprastructures of two-dimensional （2D） materials while controlling the orientation of the 2D building blocks is important in achieving large specific surface areas and tuning the ...anisotropic properties of the obtained functional hierarchical structures. In this contribution, we report that arranging graphitic carbon nitride （g-C3N4） nanosheets into one-dimensional （1D） architectures with controlled orientation has been achieved by using 1D oriented melem hydrate fibers as the synthetic precursor via a polycondensation process, during which the removal of water molecules and release of ammonia gas led to the creation of pores without destroying the 1D morphology of the oriented structures. The resulting porous g-C3N4 fibers with both meso- and micro-sized pores and largely exposed edges exhibited good sensing sensitivity and selectivity towards NO2. The sensing performance was further improved by hybridization of the porous fibers with Au nanoparticles （Au NPs）, leading to a detection limit of 60 ppb under ambient conditions. Our results suggest that the highly porous g-C3N4 fibers and the related hybrid structures with largely exposed graphitic layer edges are excellent sensing platforms and may also show promise in other electronic and electrochemical applications.
Activation of macrophages and overexpression of TNFα is associated with the pathogenesis of chronic inflammatory diseases. However, the mechanisms leading to TNFα overexpression are still unknown. ...5-methylocytosine (5-mC) is an epigenetic modification that is associated with silenced genes. Recent studies showed that it is converted to 5-hydroxylmethylocytosine (5-hmC) and reactivates gene expression through the action of the family of Ten-Eleven-Translocation (TET1-3) enzymes. In this study, we show that 5-hmC levels are increased globally and specifically in the TNFα promoter during the differentiation of monocytes to macrophages. In addition, the levels of 5-hmC are increased upon LPS stimulation of macrophages. Furthermore, CRIPSR stable knockout of TET1 decreases the expression of TNFα and other pro-inflammatory cytokines. In conclusion, we showed that TET1 contributes to the activation of macrophages possibly through regulation of 5-hydroxymethylation in the promoter of pro-inflammatory cytokine genes. The TET1 enzyme could be a promising therapeutic target to inhibit the persistent inflammation caused by macrophages in chronic inflammatory diseases.
This paper is concerned with the stochastic optimal control problem of a 1-dimensional McKean–Vlasov stochastic differential equation (SDE) with reflection, of which the drift coefficient and ...diffusion coefficient can be both dependent on the state of the solution process along with its law and control. One backward stochastic partial differential equation (BSPDE) with the Neumann boundary condition can represent the value function of this control problem. Existence and uniqueness of the solution to the above equation are obtained. Finally, the optimal feedback control can be constructed by the BSPDE.
As a coastal city with rapid urbanization and high-intensity human activities, Shenzhen, China has carried out a series of comprehensive treatments for water pollution control and ecological ...restoration in recent years. However, the restoration effect is mainly reflected in the improvement of water quality and riparian landscape, and there is still a big gap in reaching the river’s ecological restoration goals. Therefore, it is necessary to make a full investigation and evaluation of river aquatic systems that focuses on the restoration of aquatic communities and ecosystem health. We surveyed forty-seven sampling sites in nine basins to investigate water quality and aquatic organisms (algae and macroinvertebrates) during the low-water period in 2019. Under the guidance of the EU Water Framework Directive (WFD), the urban river ecosystem health assessment system, with a total of twenty indicators from six criteria layers, was established. We addressed the bioremediation objectives in this system and aquatic organism indicators as high-weight characteristic indicators. The results showed that the degradation of the river ecosystem in Shenzhen is serious, which is mainly reflected in the simple structure of the aquatic biological community and the low biodiversity. Only one “healthy” sample site, accounting for 2% of the total sampling sites; six sites of “sub-health” level, accounting for 13%; twenty-four “poor” sample points, accounting for 51%; sixteen “extremely poor” sample points, accounting for 34%. From the perspective of spatial distribution, the river ecological status of Daya Bay Basin and Dapeng Bay Basin is good, which is at the level of “health” to “sub-health”; the Guanlan River Basin, Maozhou River Basin, Shenzhen River Basin, Shenzhen Bay Basin, Pingshan River Basin, and most of the Longgang River Basin are of “poor to extremely poor” grade; the Pearl Estuary basin is of “extremely poor” grade. This assessment system can be used as an effective tool to monitor the ecological health status, especially the enhancement of biodiversity and ecosystem function of rivers. Moreover, it could provide important decision-making guidance for river management affected by high-intensity human activities.
A synthetic enzymatic pathway was designed for the deep oxidation of glucose in enzymatic fuel cells (EFCs). Polyphosphate glucokinase converts glucose to glucose-6-phosphate using low-cost, stable ...polyphosphate rather than costly ATP. Two NAD-dependent dehydrogenases (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) that were immobilized on the bioanode were responsible for generating two NADH per glucose-6-phosphate (i.e., four electrons were generated per glucose via a diaphorase-vitamin K3 electron shuttle system at the anode). Additionally, to prolong the enzyme lifetime and increase the power output, all of the recombinant enzymes that originated from thermophiles were expressed in Escherichia coli and purified to homogeneity. The maximum power density of the EFC with two dehydrogenases was 0.0203mWcm−2 in 10mM glucose at room temperature, which was 32% higher than that of an EFC with one dehydrogenase, suggesting that the deep oxidation of glucose had occurred. When the temperature was increased to 50°C, the maximum power density increased to 0.322mWcm−2, which was approximately eight times higher than that based on mesophilic enzymes at the same temperature. Our results suggest that the deep oxidation of glucose could be achieved by using multiple dehydrogenases in synthetic cascade pathways and that high power output could be achieved by using thermostable enzymes at elevated temperatures.
► A novel synthetic enzymatic pathway in enzymatic fuel cells (EFCs) can generate four electrons per glucose. ► We used polyphosphate glucokinase for converting glucose to glucose-6-phosphate without ATP. ► Thermostable enzyme-based EFCs can work well at elevated temperatures. ► Maximum power density was 0.322mWcm−2 at 50°C, eight times higher than that of mesophilic enzyme-based EFC.
To characterize the in vivo corneal epithelial thickness (CET) remodeling profile in a population of eyes after small incision lenticule intrastromal keratoplasty (SMI-LIKE) for hyperopia.
The CET ...profile was measured by RTVue-100 Fourier-domain OCT system across the central 6-mm diameter of the cornea of 17 eyes from 12 subjects (five males and seven females) who accepted corneal stromal lens implantation surgery for correcting hyperopia. The CET were measured at positions with a radius of 0-1.0 mm, 1.0-2.5 mm (divided into eight quadrants) and 2.5-3.0 mm (divided into eight quadrants) from the corneal center. Corneal maximum simulated keratometry (Km) was measured by Pentacam HR anterior segment analyzer to analyze CET changes. The examination data of subjects were collected in four time periods, which were preoperative, short-term postoperative (one week after surgery), mid-term postoperative (the last review within 3-6 months after surgery), and long-term postoperative (the last review over 1-2.5 years after surgery). The changes of CET were compared and analyzed in the four time periods.
Mean CET in 0-1.0 mm, 1.0-2.5 mm and 2.5-3.0 mm of the cornea decreased in one week after surgery, respectively, as compared to CET in the preoperative period, which turned from 55.06 ± 0.82 μm、54.42 ± 0.75 μm、53.46 ± 0.60 μm to 51.18 ± 1.05 μm (P = 0.005), 49.38 ± 0.70 μm (P = 0.000), 51.29 ± 0.59 μm (P = 0.025). In the mid-term postoperative period, mean CET in 0-1.0 mm and 1.0-2.5 mm areas kept thinner than mean CET in the preoperative period, CET in 0-1.0 mm is 50.59 ± 0.76 μm (P = 0.000),CET in 1.0-2.5 mm is 50.23 ± 0.57 μm (P = 0.000), while mean CET in 2.5-3.0 mm area recovered to the same thickness as the preoperative level, which is 54.36 ± 0.66 μm (P = 1.000), until the long-term period, CET stabilized in the above doughnut pattern.
After stromal lenticule implantation for hyperopia, CET showed a remodeled form of thinning in the 0-2.5 mm area and thickening in the 2.5-3.0 mm area, and remained stable within one year after surgery.
Dried ginger is the monarch drug in Linggan Wuwei Jiangxin (LGWWJX) decoction, which is used to treat cold asthma. The purpose of this study was to investigate and compare the effects of dried ginger ...and LGWWJX decoction for treatment of cold asthma rats at the metabolomics level using gas chromatography-mass spectrometry (GC-MS). OVA and ice water-induced cold asthma were induced in SD rats. The effects of dried ginger and LGWWJX decoction were evaluated by general morphological observation, hematoxylin and eosin staining, inflammatory cell count, IgE, IL-4, IFN-γ quantitation, and visceral index. GC-MS-based metabolomics was performed and analyzed using multivariate statistical analysis. Biomarker identification, pathway analysis, correlations between identified biomarker, and efficacy indices were performed. The results showed that dried ginger and LGWWJX decoction had obvious effects on cold asthma rats. Thirty-seven metabolites (15 in serum and 22 in urine) associated with cold asthma were identified. These metabolites were mainly carbohydrates, fatty acids and their products, organic acids, and others. Seven pathways were identified by MetaboAnalyst 4.0 metabolic pathway analysis. After intervention with dried ginger and LGWWJX decoction, the majority of altered metabolites and metabolic pathways returned to control levels. LGWWJX decoction regulated more metabolites of carbohydrates and fatty acids, which contribute to energy metabolism and oxidative stress in cold asthma, than dried ginger. We concluded that dried ginger and LGWWJX decoction both were effective for treatment of cold asthma. LGWWJX decoction was more effective than dried ginger for treatment of cold asthma. This study evaluated the effects of dried ginger and LGWWJX decoction on cold asthma at the metabolomics level. It provides a reference for the research on the compatibility of Chinese Medicine.
It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of ...mTOR-targeted therapies with sirolimus in SLE. The objective of this study was to report the successful treatment of sirolimus in a Chinese patient with refractory lupus nephritis (LN) and anti-phospholipid antibody syndrome (APS). A 44-year-old female with a previous diagnosis of autoimmune hemolytic anemia (AIHA) and APS secondary to SLE presented with lupus nephritis refractory to cyclophosphamide and mycophenolate. Renal biopsy met the criteria of WHO class III LN complicated by acute tubular injury and immunofluorescence confirmed the activation of the mTOR pathway. Treatment with the mTOR inhibitor sirolimus was initiated in this patient. Complete remission (CR) was achieved after 6 months, and flare-free remission was maintained for the next 3.5 years. The literature on the efficacy of sirolimus in patients with LN was reviewed. Although the available evidence is limited to retrospective studies with small sample sizes, sirolimus appeared to be efficacious in some patients with refractory LN. Well-designed clinical trials are warranted, and pathology-guided precision medicine might assist in guiding physicians’ treatment decisions.
Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for ...a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.
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