Cyst Reduction by Melatonin in a Novel Drosophila Model of Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the Bicaudal C (BicC) Drosophila model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the BicC fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment.     

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity,and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween^® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.     

Protective Effect of Thymus serrulatus Essential Oil on Cadmium-Induced Nephrotoxicity in Rats,through Suppression of Oxidative Stress and Downregulation of NF-κB,iNOS, and Smad2 mRNA Expression

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl₂, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl₂-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl₂ significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.     

青光眼病人口服乙酰唑胺致急性肾衰6例分析

为讨论青光眼病人口服乙酰唑胺致急性肾衰的发病几率、临床表现、发病机理及其严重性，对２１３例口服乙酰唑胺的青光眼病人进行回顾性调查。结果表明，有６例病人出现急性肾衰。可认为急性肾衰为青光眼病人口服乙酰唑胺较严重且常见的并发病，为该药的不良反应所致，临床上应予以重视。     

Protective Effects of Traditional Polyherbs on Cisplatin-Induced Acute Kidney Injury Cell Model by Inhibiting Oxidative Stress and MAPK Signaling Pathway

Acute kidney injury (AKI) is a disease caused by sudden renal dysfunction, which is an important risk factor for chronic renal failure. However, there is no effective treatment for renal impairment. Although some traditional polyherbs are commercially available for renal diseases, their effectiveness has not been reported. Therefore, we examined the nephroprotective effects of polyherbs and their relevant mechanisms in a cisplatin-induced cell injury model. Rat NRK-52E and human HK-2 subjected to cisplatin-induced AKI were treated with four polyherbs, Injinhotang (IJ), Ucha-Shinki-Hwan (US), Yukmijihwang-tang (YJ), and Urofen^TM (Uro) similar with Yondansagan-tang, for three days. All polyherbs showed strong free radical scavenging activities, and the treatments prevented cisplatin-induced cell death in both models, especially at 1.2 mg/mL. The protective effects involved antioxidant effects by reducing reactive oxygen species and increasing the activities of superoxide dismutase and catalase. The polyherbs also reduced the number of annexin V-positive apoptotic cells and the expression of cleaved caspase-3, along with inhibited expression of mitogen-activated protein kinase-related proteins. These findings provide evidence for promoting the development of herbal formulas as an alternative therapy for treating AKI.     

血液透析联合血液灌流治疗急性肾功能衰竭的临床效果分析

目的分析急性肾功能衰竭采取血液透析联合血液灌流治疗的临床效果。方法选取2010年1月—2015年1月期间惠州市中医医院收治的24例急性肾功能衰竭患者作为研究对象,按治疗方法的不同将本组患者分为两组,对照组12例患者接受单纯血液透析治疗,观察组12例患者接受血液透析联合血液灌流治疗,治疗2个月后,对两组患者的临床指标及临床效果进行统计对比。结果观察组治疗后CRP、Cr、BUN、MMS指标优于对照组,差异有统计学意义(P0.05);观察组治疗有效率为91.67%(11/12),高于对照组75.00%(9/12),差异有统计学意义(P0.05)。结论对急性肾功能衰竭患者的治疗,采取血液透析联合血液灌流治疗的临床效果显著,促进患者康复,在临床中具有良好的应用价值。     

Feasibility of similarity coefficient map for improving morphological evaluation of T2* weighted MRI for renal cancer

The purpose of this paper is to investigate the feasibility of using a similarity coefficient map(SCM) in improving the morphological evaluation of T2* weighted(T2*W) magnatic resonance imaging(MRI) for renal cancer.Simulation studies and in vivo 12-echo T2*W experiments for renal cancers were performed for this purpose.The results of the first simulation study suggest that an SCM can reveal small structures which are hard to distinguish from the background tissue in T2*W images and the corresponding T2* map.The capability of improving the morphological evaluation is likely due to the improvement in the signal-to-noise ratio(SNR) and the carrier-to-noise ratio(CNR) by using the SCM technique.Compared with T2* W images,an SCM can improve the SNR by a factor ranging from 1.87 to 2.47.Compared with T2* maps,an SCM can improve the SNR by a factor ranging from 3.85 to 33.31.Compared with T2*W images,an SCM can improve the CNR by a factor ranging from 2.09 to 2.43.Compared with T2* maps,an SCM can improve the CNR by a factor ranging from 1.94 to 8.14.For a given noise level,the improvements of the SNR and the CNR depend mainly on the original SNRs and CNRs in T2*W images,respectively.In vivo experiments confirmed the results of the first simulation study.The results of the second simulation study suggest that more echoes are used to generate the SCM,and higher SNRs and CNRs can be achieved in SCMs.In conclusion,an SCM can provide improved morphological evaluation of T2*W MR images for renal cancer by unveiling fine structures which are ambiguous or invisible in the corresponding T2*W MR images and T2* maps.Furthermore,in practical applications,for a fixed total sampling time,one should increase the number of echoes as much as possible to achieve SCMs with better SNRs and CNRs.     

A further investigation on a MALDI‐based method for evaluation of markers of renal damage

The validity of the urinary protein profile to characterize the pathological states of diabetic, nephropathic and diabetic–nephropathic patients was considered on the basis of previously obtained results by MALDI/MS, showing a different abundance ratio of the collagen α1 and α5 chain precursor fragments at m/z 1219 and 2049 and of the uromodulin precursor fragment at m/z 1912 observed in healthy subjects and patients; a larger number of subjects was examined and the obtained results were statistically evaluated. The p values related to the observed differences indicate that they are statistically significant when comparing all patients versus healthy controls, diabetic with normo or microalbuminuria versus nephropathic with advanced renal disease patients and diabetic with normo or microalbuminuria versus diabetic with advanced nephropathy patients. The scatter plot matrix gives evidence of the strict inverse relationship between the abundances of ions at m/z 1912 and 1219, the correlation coefficient being particularly high (r = 0.921, p < 0.001). The relationship between the true positive rate (sensitivity) and false positive rate (1—specificity) for every possible cutoff value in abundance of the considered ionic species was investigated through the receiver‐operating characteristic (ROC) curve. The obtained data indicate that a good differentiation of nephropathic patients with advanced renal disease and diabetic patients with advanced nephropathy versus healthy subjects can be easily obtained by this approach. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein (vFV-Apoptin) to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma(HeLa) cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetraz...