Ti─O─C Bonding at 2D Heterointerfaces of 3D Composites for Fast Sodium Ion Storage at High Mass Loading Level.

3D composite electrodes have shown extraordinary promise as high mass loading electrode materials for sodium ion batteries (SIBs). However, they usually show poor rate performance due to the sluggish Na+ kinetics at the heterointerfaces of the composites. Here, a 3D MXene-reduced holey graphene oxide (MXene-RHGO) composite electrode with Ti─O─C bonding at 2D heterointerfaces of MXene and RHGO is developed. Density functional theory (DFT) calculations reveal the built-in electric fields (BIEFs) are enhanced by the formation of bridged interfacial Ti─O─C bonding, that lead to not only faster diffusion of Na+ at the heterointerfaces but also faster adsorption and migration of Na+ on the MXene surfaces. As a result, the 3D composite electrodes show impressive properties for fast Na+ storage. Under high current density of 10 mA cm-2, the 3D MXene-RHGO composite electrodes with high mass loading of 10 mg cm-2 achieve a strikingly high and stable areal capacity of 3 mAh cm-2, which is same as commercial LIBs and greatly exceeds that of most reported SIBs electrode materials. The work shows that rationally designed bonding at the heterointerfaces represents an effective strategy for promoting high mass loading 3D composites electrode materials forward toward practical SIBs applications.

Dual-functional ionic liquids additive enables dendrite-free Zn anode with ultra-long cycle life over one year.

Zn anodes suffer from the formation of uncontrolled dendrites aggravated by the uneven electric field and the insulating by-product accumulation in aqueous zinc-ion batteries (AZIBs). Here, an effective strategy implemented by 1-butyl-3-methylimidazolium hydrogen sulfate (BMIHSO4) additive is proposed to synergistically tune the crystallographic orientation of zinc deposition and suppress the formation of zinc hydroxide sulfate for enhancing the reversibility on Zn anode surface. As a competing cation, BMI+ is proved to preferably adsorb on Zn-electrode compared with H2O molecules, which shields the "tip effect" and inhibits the Zn-deposition agglomerations to inducing the horizontal growth along Zn (002) crystallographic texture. Simultaneously, the protonated BMIHSO4 additives could remove the detrimental OH- in real-time to fundamentally eliminate the accumulation of 6Zn(OH)2·ZnSO4·4H2O and Zn4SO4(OH)6·H2O on Zn anode surface. Consequently, Zn anode exhibits an ultra-long cycling stability of one year (8762 h) at 0.2 mA cm-2/0.2 mAh cm-2, 3600 h at 2 mA cm-2/2 mAh cm-2 with a high plating cumulative capacity of 3.6 Ah cm-2, and a high average Coulombic efficiency of 99.6 % throughout 1000 cycles. This work of regulating Zn deposition texture combined with eliminating notorious by-products could offer a desirable way for stabilizing the Zn-anode/electrolyte interface in AZIBs.

Herb pair of Rhubarb-Astragalus mitigates renal interstitial fibrosis through downregulation of autophagy via p38-MAPK/TGF-ß1 and p38-MAPK/smad2/3 pathways.

BACKGROUND: Chronic kidney disease (CKD) has a high incidence and poor prognosis; however, no effective treatment is currently available. Our previous study found that the improvement effect of the herb pair of Rhubarb-Astragalus on CKD is likely related to the inhibition of the TGF-ß1/p38-MAPK pathway. In the present study, a p38-MAPK inhibitor was used to further investigate the inhibitory effect of Rhubarb-Astragalus on the TGF-ß1/p38-MAPK pathway and its relationship with autophagy. METHODS: A rat model of unilateral ureteral obstruction (UUO) was established, and a subgroup of rats was administered Rhubarb-Astragalus. Renal function and renal interstitial fibrosis (RIF) were assessed 21 d after UUO induction. In vitro, HK-2 cells were treated with TGF-ß1 and a subset of cells were treated with Rhubarb-Astragalus or p38-MAPK inhibitor. Western blotting, immunohistochemistry, and qRT-PCR analyses were used to detect the relevant protein and mRNA levels. Transmission electron microscopy was used to observe autophagosomes. RESULTS: Rhubarb-Astragalus treatment markedly decreased the elevated levels of blood urea nitrogen, serum creatinine, and urinary N-acetyl-ß-D-glucosaminidase; attenuated renal damage and RIF induced by UUO; and reduced the number of autophagosomes and lysosomes in UUO-induced renal tissues. Additionally, Rhubarb-Astragalus reduced the protein and mRNA levels of α-SMA, collagen I, LC3, Atg3, TGF-ß1, p38-MAPK, smad2/3, and TAK1 in renal tissues of UUO rats. Rhubarb-Astragalus also reduced protein and mRNA levels of these indicators in vitro. Importantly, the effect of the p38-MAPK inhibitor was similar to that of Rhubarb-Astragalus. CONCLUSIONS: Rhubarb-Astragalus improves CKD possibly by downregulating autophagy via the p38-MAPK/TGF-ß1 and p38-MAPK/smad2/3 pathways.

Macroscale preparation of CoS2 nanoparticles for ultra-high fast-charging performance in sodium-ion batteries.

Improving the fast-charging capabilities and energy storage capacity of electric vehicles presents a feasible strategy for mitigating the prevalent concern of range anxiety in the market. Nanostructure electrode materials play a crucial role in this process. However, the current method of preparation is arduous and yields restricted quantities. In view of this, we have devised an innovative approach that provides convenience and efficacy, facilitating the large-scale synthesis of CoS2 nanoparticles, which exhibited exceptional performance. When the current density was 1000 mA g-1, the discharging capacity reached 760 mAh g-1 after 400 cycles. Remarkably, even at an increased current density of 5000 mA g-1, the discharging capacity of CoS2 remained at 685.5 mAh g-1. The ultra-high performance could be attributed to the specific surface area, which minimized the diffusion distance of sodium-ions during the charging and discharging processes and mitigated the extent of structural damage. Our straightforward preparation techniques facilitate the mass production and present a novel approach for the development of cost-effective and high-performing anode materials for sodium-ion batteries.

Economic synthesis of sub-micron brick-like Al-MOF with designed pore distribution for lithium-ion battery anodes with high initial Coulombic efficiency and cycle stability.

Metal-organic frameworks (MOFs) have exhibited great potential for lithium-ion batteries (LIBs). However, to date, it is difficult to fabricate MOF electrode materials with regular shape and rational pore distribution by an economic approach, and the currently achieved MOF electrode materials usually have a relatively low initial Coulombic efficiency and poor cycle stability, which is not satisfactory for practical application. In this study, by using the recycled AlCl3 solution after dealloying treatment of Al-Si alloy, an evenly distributed brick-like Al-MOF with sub-micron size and rational pore distribution was synthesized for the first time. Because of the larger size and more macropores, the as-prepared Al-MOF electrode exhibits superior initial Coulombic efficiency as high as 96.6% for LIB anodes. Moreover, on account of the irregular crystal defects at the edge of the designed macropores, which result from unstable connection between the inorganic nodes (AlO6 octahedral cluster) and the organic linkers (PTA) and result in the formation of spherical nano-sized particles with better structural stability, the electrode materials show excellent cycle stability with discharge attenuation rate of 0.051%. The electrochemical performance considerably outperforms that of reported Al-MOF anodes and some representative MOF anodes in other studies. The robust realization of high initial Coulombic efficiency and cycle stability defines a critical step to capturing the full potential of MOF electrode materials in practical LIBs.

Ginkgo biloba leaf extract mitigates cisplatin-induced chronic renal interstitial fibrosis by inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells mediated by the Smad3/TGF-ß1 and Smad3/p38 MAPK pathways.

BACKGROUND: Our previous study indicated that Ginkgo biloba leaf extract (EGb) could protect against cisplatin-induced acute kidney injury in rabbits. The present study aimed to determine the effects and potential molecular mechanisms of EGb on chronic renal interstitial fibrosis induced by cisplatin using in vivo and in vitro models. METHODS: Rats received a single dose of cisplatin on Day 1, and a subset of rats was intraperitoneally injected with EGb daily between Days 22-40. In vitro, HK-2 cells were treated with cisplatin, and a subset of cells was cultivated with EGb or SIS3 (Smad3 inhibitor) for 48 h. Renal function of rats was assessed by detecting the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-ß-D-glucosaminidase (NAG). Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the damage and fibrosis of renal tissue. Western blotting, immunohistochemistry and immunofluorescence were used to detect the protein levels of fibrosis-associated proteins and signaling pathway-related proteins. RT-qPCR analysis was used to examine the mRNA levels of related indicators. RESULTS: EGb significantly decreased the increased levels of Scr, BUN and urinary NAG and attenuated renal damage and the relative area of renal interstitial fibrosis induced by cisplatin. Additionally, EGb decreased the protein levels of α-SMA, Col I, TGF-ß1, smad2/3, phosphorylated (p)-smad2/3, p38 MAPK, and p-p38 MAPK; the ratio of p-p38 MAPK/p38 MAPK; and the mRNA level of p38 MAPK in renal tissues induced by cisplatin. In agreement with in vivo studies, EGb significantly reduced the increased protein levels of these indicators. Additionally, EGb significantly reduced the increased protein levels of vimentin, TIMP-1, and CTGF, as well as the mRNA levels of α-SMA, vimentin, and TGF-ß1, while it significantly increased the reduced E-cadherin protein level and the MMP-1/TIMP-1 ratio in HK-2 cells induced by cisplatin. It's worth noting that the effects of SIS3 in changing the above indicators were similar to those of EGb. CONCLUSION: Our study demonstrated that EGb improved cisplatin-induced chronic renal interstitial fibrosis, and its mechanisms were associated with inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells via the Smad3/TGF-ß1 and Smad3/p38 MAPK pathways.

Panax notoginseng saponins reduces the cisplatin-induced acute renal injury by increasing HIF-1α/BNIP3 to inhibit mitochondrial apoptosis pathway.

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1α in the rat model, according to the data from our previous works. However, the underlying link between HIF-1α and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1α-dependent apoptosis. A stably HIF-1α-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1α-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1α-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1α-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1α to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.

Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-ß1/p38MAPK/Smad2/3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L; Astragalus membranaceus (Fisch.), is referred to as 'Dahuang, Huangqi' in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. AIM OF THE STUDY: This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. MATERIALS AND METHODS: Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-ß1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. RESULTS: The drug-containing serum of rhubarb-astragalus contained emodin (0.36 µg/ml) and danthraquinone (0.96 µg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-ß1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-ß1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-ß1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-ß1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-ß1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. CONCLUSION: The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-ß1/p38 MAPK/Smad2/3 pathway.

Ginaton injection alleviates cisplatin-induced renal interstitial fibrosis in rats via inhibition of apoptosis through regulation of the p38MAPK/TGF-ß1 and p38MAPK/HIF-1α pathways.

Ginaton injection (Ginkgo biloba extract; GBE) has been reported to protect against cisplatin-induced acute renal failure in rats. In the present study, the effects and molecular mechanisms of GBE on cisplatin-induced renal interstitial fibrosis were evaluated using a rat model. The rats were intraperitoneally injected with cisplatin once on the first day and a subset of rats were treated with GBE or SB203580 (SB; a specific p38 MAPK inhibitor) daily from days 22 to 40. The levels of N-acetyl-ß-D-Glucosaminidase (NAG) in the urine, and of urea nitrogen (BUN) and creatinine (Scr) in the blood were assessed. The damage and fibrosis of renal tissues were evaluated using hematoxylin and eosin staining, as well as Masson's trichrome staining, respectively. Apoptosis in renal tissues was detected using a TUNEL assay. The protein expression levels of α-smooth muscle actin (SMA), collagen 1 (Col I), Bax, Bcl-2, caspase-3/cleaved caspase-3, hypoxia-inducible factor-1α (HIF-1α), TGF-ß1 and p38MAPK, as well as the mRNA levels of p38MAPK in renal tissues were investigated. The results showed that GBE markedly reduced the levels of urinary NAG, Scr and BUN, and renal expression of α-SMA and Col I levels were also reduced. Furthermore, GBE significantly reduced renal tissue injury and the relative area of renal interstitial fibrosis induced by cisplatin. GBE effectively reduced the apoptotic rate of renal tissues, the protein expression levels of Bax, cleaved caspase-3, phospho-p38MAPK, TGF-ß1 and HIF-1α, as well as the mRNA expression levels of p38MAPK in renal tissues induced by cisplatin, whereas GBE significantly increased Bcl-2 protein expression. SB exhibited similar effects to GBE, although it was not as effective. In summary, the present study is the first to show that GBE significantly alleviated renal interstitial fibrosis following cisplatin-induced acute renal injury. The mechanisms by which GBE exhibited its effects were associated with the inhibition of apoptosis via downregulation of the p38MAPK/TGF-ß1 and p38MAPK/HIF-1α signaling pathways.

Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-ß1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway.

BACKGROUND Rhubarb and astragalus capsule (RAC) has been used in the clinical treatment of chronic kidney disease for decades. However, the mechanism of RAC has not been fully elucidated. This study aimed to investigate the protective effect and mechanisms of RAC on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. MATERIAL AND METHODS The main components of RAC are detected by high-performance liquid phase (HPLC). A rat model of UUO was established, and a subset of rats underwent treatment with RAC. Renal function and renal pathology were examined at 14 days and 21 days after the UUO operation. Renal cell apoptosis was detected by TUNEL staining. The levels of Bcl-2 and Bax in the kidney were examined by western blotting, and the levels of collagen I, alpha-SMA, transforming growth factor (TGF)-ß1, and p38 MAPK in the kidneys were detected by immunohistochemistry. RESULTS High-performance liquid phase chromatography showed that RAC contained 1.12 mg/g aloe-emodin, 2.25 mg/g rhein, 1.75 mg/g emodin, and 4.50 mg/g chrysophanol. Administration of RAC significantly decreased the levels of urinary N-acetyl-ß-D-glucosaminidase (NAG), serum blood urea nitrogen (BUN), and creatinine (Scr) and also reduced renal tissue damages and interstitial fibrosis induced by UUO in rats. Moreover, the increased levels of collagen I, alpha-SMA, TGF-ß1, p38 MAPK, and the Bax/Bcl-2 ratio, as well as cell apoptosis in the kidney, were induced by UUO, and were all found deceased by RAC treatment. CONCLUSIONS RAC can improve the renal interstitial fibrosis induced by UUO, and the mechanism may be related to inhibition of renal tubular cell apoptosis via TGF-ß1/p38 MAPK pathway.

Panax notoginseng saponins ameliorate cisplatin-induced mitochondrial injury via the HIF-1α/mitochondria/ROS pathway.

Cisplatin is a major antineoplastic drug that is used to treat solid tumors, but its use is restricted by its nephrotoxicity. Such cisplatin-induced nephrotoxicity (CIN) is believed to occur primarily through mitochondrial damage and reactive oxygen species (ROS) generation. Our previous studies have indicated that Panax notoginseng saponins (PNSs) mitigate CIN by enhancing hypoxia-inducible factor 1α (HIF-1α)-induced mitochondrial autophagy. In this study, the role of the HIF-1α/mitochondria/ROS pathway in PNSs protection against CIN was investigated using a rat model. A CIN model was generated by giving rats intraperitoneal injections with cisplatin (a single dose) and then treating them with or without 2-methoxyestradiol (HIF-1α inhibitor) and PNSs. We then measured ROS levels, superoxide dismutase, glutathione, catalase malondialdehyde and nitric oxide (to evaluate oxidative stress) and ATP, mitochondrial membrane potential and mitochondrial permeability transition pore opening (to evaluate mitochondrial function) in kidneys at different time points. We observed that PNSs remarkably reduced the levels of ROS, malondialdehyde and nitric oxide, as well as the opening of mitochondrial permeability transition pore, which is increased by cisplatin and further increased by HIF-1α inhibition. In addition, PNSs increased the levels of superoxide dismutase, catalase and glutathione, as well as ATP and mitochondrial membrane potential in renal tissues; these are all reduced by cisplatin and further reduced by HIF-1α inhibition. In conclusion, we demonstrate here that PNSs protects against mitochondrial damage induced by cisplatin through HIF-1α/mitochondria/ROS.

Naproxen for the treatment of neoplastic fever: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: The effect of naproxen on the treatment of neoplastic fever is still unclear. A systematic review and meta-analysis were performed to investigate the effect of naproxen in the treatment of cancer fever or suspicion. Besides, the latest and most convincing evidence was provided for the earlier use of naproxen in treating cancer patients with fever of unknown origin. METHODS: A literature review was conducted to identify all published studies on the naproxen for the treatment of neoplastic fever. Electronic databases (eg, PUBMED, EMBASE and the Cochrane Library) were searched until October 2018. Data were extracted, and the risk of bias was assessed by 2 authors independently. Standard meta-analyses on the rate of successful treatment were conducted using a random-effects model, and relative risks were calculated with 95% confidence intervals (CIs). RESULTS: A total of 15 studies, recruiting 582 participants, were included, which were 1 randomized controlled trial (RCT), 1 non-RCT, 3 cross-sectional studies, and 10 case-series studies. The result of our meta-analysis revealed that the success rate on the treatment of neoplastic fever using naproxen was 94.1% (95% CI: 87.6%-97.3%). The success rate of the suspected neoplastic fever was 79.8%; for fever of unknown origin, it also reached 67.7%. In this meta-analysis, the success rate was 98.1% (95% CI: 95.0%-99.3%) in the dosage of 250 mg twice a day. Besides, a small dose of 125 mg naproxen, 375 mg twice a day and 250 mg 3 times a day were also useful. The result of the subgroup analysis revealed that the difference was not statistically significant in the treatment success rate for solid tumors and hematologic malignant. CONCLUSIONS: The result of our meta-analysis suggested that naproxen exhibited a highly successful rate for the treatment of neoplastic fever. Besides, naproxen was also satisfactory in improving symptoms of suspected neoplastic fever and fever of unknown origin. The earlier use of naproxen might be able to mitigate cancer patient's suffering and enhanced their quality of life. These findings, however, rely primarily on observational data and should be interpreted rigorously. Further well-conducted trials are required to assess naproxen for the treatment of neoplastic fever.

Effects of Kudingcha Nanoparticles in Hyperlipidaemic Rats Induced by a High Fat Diet.

BACKGROUND/AIMS: The herbal medicine Kudingcha has a bitter taste and low bioavailability for lipid reduction. To improve the bioavailability and ameliorate the compliance, we prepared Kudingcha nanoparticles and investigated their effect in hyperlipidaemic rats. In addition, the safety and lipid-lowering mechanism of the Kudingcha nanoparticles were examined. METHODS: Kudingcha nanoparticles were prepared by ionotropic gelation and spray-drying. Seventy rats were randomly assigned into eight groups: a normal fat diet group (NF), a high-fat group (HF), a spontaneous recovery group (SR), a Kudingcha group (KDC), a blank nanoparticle group (B-N), and a Kudingcha nanoparticle groups (low, medium and high doses). All groups (except for the normal fat diet group) were fed a high-fat diet to establish hyperlipidaemia. Different interventions were administered to the treatment groups for four weeks. Serum lipids were measured using commercially available kits according to the recommended protocols. Liver morphology and histopathology were examined by a light microscope. The mRNA and protein levels of TLR4 and NF-κB were determined by RT-PCR and Western blotting, respectively. In addition, acute toxicity was evaluated by the LD50 test. RESULTS: The Kudingcha nanoparticles were spherical and had a smooth surface. The size distribution of the nanoparticles was 100-600 nm. Acute toxicity results revealed that the Kudingcha nanoparticles were a non-toxic substance. Compared with regular Kudingcha, TG and TC decreased distinctly in the Kudingcha nanoparticles, especially for the moderate and high dose groups (p<0.05). Moreover, the Kudingcha nanoparticles were superior in lowering body, liver and adipose tissue weights compared to Kudingcha (p<0.05). With respect to antioxidant properties, the nanoparticles also revealed an outstanding impact on serum SOD and MDA. In addition, liver morphology and histology in the moderate and high dose nanoparticle groups were similar to those in the normal group. Finally, the mRNA and protein expression levels of TLR4 and NF-κB in the liver tissue of the nanoparticle groups were significantly upregulated compared with the KDC group (p<0.05). CONCLUSIONS: Based on these results, we conclude that Kudingcha nanoparticles are a potent lipid-lowering agent and may have a potential role in the treatment of hyperlipidaemia and fatty liver disease.

Rutaecarpine Suppresses Proliferation and Promotes Apoptosis of Human Pulmonary Artery Smooth Muscle Cells in Hypoxia Possibly Through HIF-1α-Dependent Pathways.

PURPOSE: The aim of this study is to investigate the potential roles of Rutaecarpine (Rut) in hypoxia-induced human pulmonary artery smooth muscle cells (HPASMCs) model. METHODS: HPASMCs were cultured with or without hypoxia followed by Rut administration. Cytotoxicity and cell proliferation were assessed by CCK-8 and Cell counting method. Flow cytometry was used for the measurement of cell apoptosis rates. The mRNA expression of hypoxia-induced factor (HIF)-1α and protein levels of HIF-1α, p53, p21, erythropoietin, and vascular endothelial growth factor were determined by quantitative real-time polymerase chain reaction and Western blot, respectively. RESULTS: Rut inhibited the proliferation of HPASMCs with IC50 value of 43.5 µmol·L. Hypoxia significantly increased proliferation and decreased apoptosis in HPASMCs, whereas Rut rescued this phenomenon at the appropriate concentration. Meanwhile, Rut effectively decreased the protein and mRNA expressions of HIF-1α. Knockdown of HIF-1α expression by small interfering RNA (siRNA) significantly enhanced the proapoptotic effect rather than antiproliferation effect of Rut in HPASMCs. Moreover, Rut simultaneously reduced proliferating cell nuclear antigen protein expression, whereas increased p53 and p21 protein levels. However, no significant difference was observed in the protein levels of vascular endothelial growth factor and erythropoietin. CONCLUSIONS: Our results demonstrated that Rut exerted protective effects on HPASMCs against hypoxia partly through the HIF-1α-dependent signaling pathway.

Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.

We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by Panax notoginseng saponins (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-ß-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1α mRNA and nuclear localized HIF-1α protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1α, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1α/BNIP3/Beclin-1 signaling pathway.

THE ANTIBACTERIAL EFFECT OF URENA LOBATA L. FROMV GUANGXI ON MICE WITH STAPHYLOCOCCUS AUREUS PNEUMONIA.

BACKGROUND: Alcohol extract from the root of Urena lobata L. (ULL) had broad spectrum antimicrobial activity. Studies in vitro have sho that ULL aqueous extract has antibacterial effect on S. aureusis, and the combination therapy of the ULL aqueous extract with cefazolin sodium showed additive effect. MATERIALS AND METHODS: The mice underwent nasal inhalation with S. aureus, a subset of mice were intra-gastric gavage with ULL and/or intravenous injection cefazolin sodium twice daily. After being exposed to S. aureus for 5 days, 10 days and 14 days respectively, the white blood cells count (WBC), neutrophils absolute value (NEU) and the neutrophil percentage (NEU%) in peripheral blood, as well as the levels of serum immunoglobulin (Ig) G and IgM were determined using commercial kits. The colony count of S. aureus, the levels of interleukin (IL) -6 and IL-10 of mice lung tissue were detected, and the pathological changes of lung tissue were examined using H & E staining. RESULTS: ULL significantly protected against S. aureus pneumonia, as evidenced by the remarkable decrease in the rate of S. aureus colony count/lung weight, WBC, NEU and NEU% in peripheral blood, as well as the attenuation of lung histopathological damage. Additionally, ULL+cefazolin could have markedly reduced the rate of S. aureus colony count/lung weight when compared with cefazolin. Furthermore, ULL and ULL+cefazolin both could significantly decrease the serum levels of IgG and IgM, and the levels of IL-6, IL-10 in mice lung tissue. CONCLUSION: This study first demonstrated that ULL may have potential use as a therapeutic agent for S. aureus pneumonia, and the roles of IgG, IgM, IL-6 and IL-10 in ULL protection against S. aureus pneumonia remain to be further studied.

Comparison of quality of life in homeless and non-homeless Chinese patients with psychiatric disorders.

To date, there are no data on quality of life (QOL) and its correlates in homeless Chinese patients with psychiatric disorders. This study aimed to compare QOL between homeless and non-homeless patients with psychiatric disorders in China. A total of 278 homeless and 222 non-homeless patients matched in age and gender were consecutively recruited. Socio-demographic and clinical data were collected from medical records. A clinical interview was conducted using standardized instruments. The physical and mental QOL in both groups were lower than the normative data for Chinese general population, but there was no significant difference in any QOL domain between the two groups. Multivariate analyses of homeless patients revealed that male gender was associated with higher physical QOL, while living in cities and lower education level were associated with higher mental QOL. In non-homeless patients, use of second-generation antipsychotics was associated with lower physical QOL, while having more severe depressive symptoms was associated with lower mental QOL. Longitudinal studies are warranted to clarify the contributing factors of QOL in both homeless and non-homeless patients.

Sulfonylurea for the treatment of neonatal diabetes owing to KATP-channel mutations: a systematic review and meta-analysis.

The effect of sulfonylurea for the treatment of neonatal diabetes (NDM) is remain uncertain. We conducted this systematic review and meta-analysis to investigate the effect of sulfonylurea for NDM and to provide the latest and most convincing evidence for developing clinical practice guidelines of NDM. A literature review was performed to identify all published studies reporting the sulfonylurea on the treatment of neonatal diabetes. The search included the following databases: PUBMED, EMBASE and the Cochrane Library. The primary outcome was the success rates of treatment, change of glycosylated hemoglobin (HbA1c) and C-peptide. Data results were pooled by using MetaAnalyst with a random-effects model. Ten studies (6 cohort studies and 4 cross-sectional studies) involving 285 participants were included in the analysis. The pooled estimated success rate by the random-effects model was 90.1%(95% CI: 85.1%-93.5%). HbA1c had a significantly lower compared with before treatment. The pooled estimate of MD was -2.289, and the 95% CI was -2.790 to -1.789 (P < 0.001). The subgroup analysis showed a similar result for cohort studies and in cross-sectional studies. The common mild side effect is gastrointestinal reaction. The present meta-analysis suggested that sulfonylurea had a positive effect for treatment NDM due to KATP channel mutations. In addition, sulfonylurea also displayed sound safety except the mild gastrointestinal reaction. However, the findings rely chiefly on data from observational studies. Further well-conducted trials are required to assess sulfonylurea for NDM.

Hierarchical TiO2 spheres as highly efficient polysulfide host for lithium-sulfur batteries.

Hierarchical TiO2 micron spheres assembled by nano-plates were prepared through a facile hydrothermal route. Chemical tuning of the TiO2 through hydrogen reduction (H-TiO2) is shown to increase oxygen-vacancy density and thereby modifies the electronic properties. H-TiO2 spheres with a polar surface serve as the surface-bound intermediates for strong polysulfides binding. Under the restricting and recapturing effect, the sulfur cathode could deliver a high reversible capacity of 928.1 mA h g(-1) after 50 charge-discharge cycles at a current density of 200 mA g(-1). The H-TiO2 additive developed here is practical for restricting and recapturing the polysulfide from the electrolyte.

Effects of chitosan and water-soluble chitosan micro- and nanoparticles in obese rats fed a high-fat diet.

PURPOSE: This study determined the effects of chitosan (CTS) and water-soluble chitosan (WSC) microparticles (MPs) and nanoparticles (NPs) in rats with high-fat diet-induced obesity. METHODS: THE RATS WERE RANDOMLY SEPARATED INTO EIGHT GROUPS: a normal diet group (the blank control), a high-fat emulsion group (the negative control), CTS and WSC control groups, CTS-MP and WSC-MP groups, and CTS-NP and WSC-NP groups. All groups (except the blank control group) were fed the high-fat diet for 4 weeks to establish the obesity model. Different samples were administered orally once daily to the treatment groups for 4 weeks. RESULTS: A significantly lower weight gain was observed in the WSC-MP and WSC-NP groups, as well as in the CTS-MP and CTS-NP groups, compared with rats given a normal diet and a high-fat diet (P < 0.05). The WSC-MP rats had the least weight gain among all the groups. The food intake in the eight groups had the same trend as weight gain. CTS and WSC MPs and NPs significantly reduced the final amounts of epididymal and perirenal white adipose tissue. Liver weight was reduced in the CTS-MP group compared to rats fed a high-fat diet. Serum total cholesterol and low-density lipoprotein cholesterol were significantly reduced in all treatment groups, with the WSC-MP and CTS-MP groups showing a more significant reduction than the other groups. Triacylglycerol levels were significantly reduced in the WSC-NP group compared to the high-fat group. The mortality rates of CTS-MP, CTS-NP, WSC-MP, and WSC-NP groups were 30%, 30%, 55%, and 65%, respectively. The median lethal dose for the WSC-MP and WSC-NP groups were 4080 mg/kg and 2370 mg/kg, respectively. CONCLUSION: These results indicate that CTS and WSC MPs and NPs have greater effects than commercially available CTS and WSC, and can be used as potential antiobesity agents.