Exercise-Mediated Alteration of miR-192-5p Is Associated with Cognitive Improvement in Alzheimer's Disease.

INTRODUCTION: Physical exercise is an important component of managing Alzheimer's disease (AD). miRNAs can be modulated by exercise intervention. OBJECTIVE: The study explored the involvement and potential mechanism of miR-192-5p in the protective effect of physical exercise on AD. METHODS: Ninety AD patients were enrolled, in which 45 cases accepted cycling training for continuous 3 months. The expression changes of miR-192-5p before and after exercise were analyzed by reverse transcription-quantitative PCR. 8-month-old APP/PS1 double Tg mice were used as the AD animal model. Mice in the voluntary exercise (VE) group received VE for 4 weeks. Morris water maze (MWM) test was used to evaluate the learning and memory function. Enzyme-linked immunosorbent assay was used to calculate the level of IL-1ß, IL-6, and TNF-α. RESULTS: AD patients showed elevated MMSE scores, decreased ADAS-cog and NPI-Q scores after 3 months of exercise. miR-192-5p was downregulated in the serum of AD patients and correlated with the levels of MMSE score, ADAS-cog, and NPI-Q score. A positive association was detected between serum miR-192-5p with TNF-α, IL-6, and IL-1ß levels. MiR-192-5p is downregulated in the hippocampus tissues of mice after VE. Overexpression of miR-192-5p reversed the neuroprotective effect of exercise on AD in mice and promoted the inflammatory response of AD mice. CONCLUSION: MiR-192-5p can be modulated by the exercise intervention and involved in the protective effect of exercise on AD.

Polycyclic aromatic hydrocarbons in soils of Central Plains Urban Agglomeration, China: The bidirectional effects of urbanization and anthropogenic activities.

To investigate the variations in environmental behavior (levels, distribution, sources, and soil toxicity) of polycyclic aromatic hydrocarbons (PAHs) under the impact of anthropogenic activities during the urbanization process, we collected soil samples from 195 sites in the Central Plains Urban Agglomeration (CPUA), North China, and analyzed 16 U.S. Environmental Protection Agency (EPA) PAH priority pollutants. We divided the sampling sites into three groups (urban area, industrial area, and farmland) and collected soil samples (0-20 cm surface layer). ∑16PAHs concentrations in the soils of the urban area, industrial area, and farmland ranged from 24.2 to 4400 ng/g, 12.3-8780 ng/g, and 20.9-852 ng/g (the average value of 349, 634, and 186 ng/g), respectively. The 4 to 5 ring PAHs were dominant compounds in three soil types, accounting for 65-80% of the ∑16PAHs. The results of the source analysis showed that the PAHs in the soils of CPUA were mainly from energy consumption. PAH levels in urban and industrial soils had a potential low cancer risk. The impact of urbanization on PAHs in the soil was bidirectional. On the one hand, the level of PAHs in the farmland soil might increase due to burning coal and agricultural machinery, which releases diesel or petrol fumes. On the other hand, in the urbanization process, the PAH content in urban soil and industrial soil showed a downward trend due to the implementation of environmental protection policies in China, which have reduced the atmospheric input of PAHs into the soil.

ß-Asarone increases doxorubicin sensitivity by suppressing NF-κB signaling and abolishes doxorubicin-induced enrichment of stem-like population by destabilizing Bmi1.

BACKGROUND: Lymphoma is one of the most common hematologic malignancy. Drug resistance is the main obstacle faced in lymphoma treatment. Cancer stem cells are considered as the source of tumor recurrence, metastasis and drug resistance. The ß-Asarone, a low-toxicity compound from the traditional medical herb Acorus calamus, has been shown to act as an anti-cancer reagent in various cancer types. However, the anti-cancer activities of ß-Asarone in lymphoma have not been shown. METHODS: Cell counting assay was used to evaluate Raji cell proliferation. CCK8 assay was used to evaluate the cell viability. Annexin-V/PI staining and flow cytometry analysis were used to evaluate apoptosis. ALDEFLUOR assay was used to evaluate the stem-like population. Luciferase reporter assay was used to examine the activation of NF-κB signaling. Western blot and polymerase chain reaction (PCR) were used to determine the expression of interested genes. RESULTS: We showed that ß-Asarone inhibited proliferation and induced apoptosis in Raji lymphoma cells in a dose-dependent manner. Additionally, ß-Asarone functioned as a sensitizer of doxorubicin and resulted in synergistic effects on inhibition of proliferation and induction of apoptosis when combined with doxorubicin treatment. Interestingly, we found that ß-Asarone also reduced the stem-like population of Raji lymphoma cells in a dose-dependent manner, and suppressed the expression of c-Myc and Bmi1. Importantly, ß-Asarone abolished doxorubicin-induced enrichment of the stem-like population. In the mechanism study, we revealed that ß-Asarone suppressed not only basal NF-κB activity but also Tumor necrosis factor α (TNF-α) induced NF-κB activity. Moreover, blocking NF-κB signaling inactivation was critical for ß-Asarone induced apoptosis and inhibition of proliferation, but not for the effect on ß-Asarone reduced stem-like population. In fact, ß-Asarone suppressed stem-like population by destabilizing Bmi1 via a proteasome-mediated mechanism. CONCLUSIONS: Our data suggested the application of ß-Asarone to lower the toxic effect of doxorubicin and increase the sensitivity of doxorubicin in clinical treatment. More importantly, our data revealed a novel role of ß-Asarone which could be used to eliminate stem-like population in lymphoma, implying that ß-Asarone might reduce relapse and drug resistance.

Complexation of Lanthanides with N, N, N', N'-Tetramethylamide Derivatives of Bipyridinedicarboxylic Acid and Phenanthrolinedicarboxylic Acid: Thermodynamics and Coordination Modes.

The thermodynamics of Nd(III) and Eu(III) complexes with N, N, N', N'-tetramethyl-2,2'-bipyridine-6,6'-dicarboxamide (TMBiPDA) and N, N, N', N'-tetramethyl-1,10-phenanthroline-2,9-dicarboxamide (TMPhenDA) in CH3OH/10%(v)H2O solutions were studied. Stability constants and enthalpies of complexation were determined by absorption spectrophotometry, luminescence, and calorimetry. The stability constants of corresponding lanthanide complexes decrease in the order of TMPhenDA > TMBiPDA, while those of the corresponding ligand complexes with lanthanides decrease in the order of Nd(III) > Eu(III). The stepwise reactions for all 1:1 complexes as well as for the 1:2 Nd(III) complexes are driven by both enthalpy and entropy, while those for the 1:2 Eu(III) complexes are driven by entropy. The stronger affinity of TMPhenDA to Nd(III) and Eu(III) than that of TMBiPDA is predominantly arisen from its high preorganization. The spectra of the complexes in solutions are similar, implying that Nd(III) and Eu(III) coordinate with the two ligands in the same mode, which have been validated by 1H and 13C NMR titrations using La(III) as lanthanide tracer. The luminescence lifetimes of the Eu(III) complexes with TMBiPDA and TMPhenDA were evaluated by TRLFS. Structures of Nd(III)/TMPhenDA and Eu(III)/TMPhenDA complexes, identified by single-crystal X-ray diffractometry, show that ligand coordinates to metal in a tetradentate mode via two aromatic N-donors and two amide O-donors, and the central cation (Nd(III) or Eu(III)) is 10-coordinated by two whole TMPhenDA and two solvent (water or methanol) molecules. The M-O bond distances are almost identical, while the Nd-N bond distance is shorter than the Eu-O bond.

Occurrence and Estrogenic Potency of Bisphenol Analogs in Sewage Sludge from Wastewater Treatment Plants in Central China.

Land application is suggested to be the most economical sludge disposal method but is also a potential source of bisphenol analogs (BPs) to the environment. In this study, BP concentrations in sewage sludge from Henan province ranged from 15.1 to 2237 ng g-1 dw. BPA was dominant with mean concentration of 140 ng g-1 dw, followed by BPS (mean 43.4 ng g-1 dw), BPF (mean 7.98 ng g-1 dw), BPAF (mean 1.04 ng g-1 dw), BPAP (mean 0.88 ng g-1 dw), BPB (mean 0.38 ng g-1 dw), and BPZ (mean 0.33 ng g-1 dw). Apart from BPB, no significant correlations were found between BPs and wastewater treatment plants characteristics, probably because adsorption does not play a major role in the removal of BPs. The estimated total emission flux of BPs from sludge-amended soils are approximately 62.7 kg year-1. BPA is the largest contributor with emission flux of 45.3 kg year-1. Hazard quotient values for BPs in sludge-amended soils are 3-6 orders of magnitude lower than 1 with total 17ß-estradiol equivalents ranging from 0.33 to 26.8 pg g-1 E2EQ dw. Overall, although being partially replaced by other analogs, BPA is still widely used in Henan province.

Exo â ¢-assisted amplification signal strategy synergized with Au@Pt NFs/CoSe2 for sensitive detection of enrofloxacin.

Overuse of enrofloxacin (ENR) has posed a potential threat to ecosystems and public health, so it is critical to sensitive and accurate determination of ENR residues. In this work, a novel ultra-sensitive and specific electrochemical aptasensor was fabricated based on the cobalt diselenide loaded gold and platinum nanoflowers (Au@Pt NFs/ CoSe2) and Exonuclease III (Exo III)-assisted cycle amplification strategy for the detection of ENR. Au@Pt NFs/ CoSe2 nanosheets as the substrate material, with large surface area, accelerate electron transfer and attach more DNA probes on the electrode substrate, have effectively enhanced the electrochemical performance of the electrode. With the existence of Enrofloxacin (ENR), the aptamer recognizes and binds to ENR, thus the signal probe cDNA was released and immobilized onto the electrode surface to hybridized with methylene blue (MB) labelled DNA (MB-DNA), thereby triggering the Exo III-assisted cycle for further signal amplification. As expected, the prepared aptasensor demonstrated excellent sensitivity and selectivity, with a wide linear range from 5.0 × 10-6 ng/mL to 1.0 × 10-2 ng/mL for ENR, a low detection limit of 1.59 × 10-6 ng/mL. Consequently, this strategy provided a promising avenue for ultrasensitive and accurate detection of ENR in milk samples.

Effects of compound Danshen dropping pills on adverse cardiovascular events and quality of life after percutaneous coronary intervention in patients with coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) is an important means for the treatment of coronary atherosclerotic heart disease and has effectively reduced the mortality of coronary heart disease. However, reperfusion can also cause certain damage to the vascular endothelium, leading to the major adverse cardiovascular events. Compound Danshen dropping pill is a Chinese patent medicine preparation. At present, many studies have evaluated the effect of compound Danshen dropping pill in reducing the incidence of adverse cardiovascular events after PCI. This study systematically evaluated the effect of compound Danshen dropping pills on major adverse cardiovascular events and quality of life after PCI and provides a reference for clinical application and research. METHODS: All randomized controlled trials on the effects of compound Danshen dropping pills on adverse cardiovascular events and quality of life after PCI for coronary heart disease were searched for. The search was conducted from database inception to January 2022. Data extraction and quality assessment were performed by 2 reviewers according to the Protocol Guidelines for Systematic Reviews and Meta-analyses Protocols statement guidelines. Meta-analysis was performed using Review Manager Version 5.4 software and Stata 16 software. RESULTS: The results of this study will allow for systematically evaluation of the effects of compound Danshen dropping pills on adverse cardiovascular events and quality of life after PCI for coronary heart disease. CONCLUSION: This study will provide objective evidence of a basis for compound Danshen dropping pills reducing adverse cardiovascular events and improving quality of life after PCI.

Spatiotemporal evolution law and driving force of mining city patterns.

Urban transformation is an inevitable trend for mining cities to achieve sustainable development. Analyzing the spatiotemporal evolution laws and driving mechanisms of mining cities is necessary for providing a scientific basis for their transformation. In this study, Jixi was taken as an example, which is a typical mining city in China. Based on geographic information system, various mathematical statistical analysis methods were used to quantitatively analyze the evolution pattern of mining cities. In addition, the driving mechanisms of land expansion in mining cities were examined further. The results showed that (1) the urban land in the mining city is mainly distributed in low-lying areas, and land expansion mainly occurred in flat areas. (2) Based on the distribution of mineral resources, the land use pattern of mining cities was scattered; with steady economic development, the urban spatial pattern tends to be compact. (3) The spatial pattern of mining cities is affected by natural, economic, and policy factors. The results reveal the spatiotemporal evolution law and driving mechanism of the patterns in mining cities, thereby providing a scientific basis for the sustainable development planning and land management of mining cities.

Au@ZnNi-MOF labeled electrochemical aptasensor for detection of enrofloxacin based on AuPt@h-CeO2/MoS2 and DNAzyme-driven DNA walker triple amplification signal strategy.

Herein, an aptasensor based on Pb2+ dependent DNAzyme driven DNA Walker with the triple amplification signal strategy was developed for ultrasensitive detection of enrofloxacin (ENR). The composite of Au & Pt coated hollow cerium oxide (AuPt@h-CeO2), and polyethyleneimine (PEI) functionalized molybdenum disulfide (PEI-MoS2) were used as the substrate material to increase the specific surface area of the electrode and attach more DNA probes. In the presence of ENR, the aptamer can break away from the double-stranded structure, releasing DNAzyme capable of cleaving circular RNA with the help of Pb2+, which in turn will generate a large number of capture probes that bind the signal probes. In-situ reduced gold nanoparticles coated bimetallic metal-organic framework (Au@ZnNi-MOF) as signal labeled to catalyze thionine (Thi) to amplify the signal, which could be observed a significant electrochemical signal in square wave voltammetry (SWV). As expected, under the optimal conditions, the current in SWV is linearly related with the concentration of ENR in the range of 5.0 × 10-6 to 1.0 × 10-2 ng/mL with a limit of detection of 1.02 × 10-7 ng/mL. Further, it has been successfully used in real environmental water and milk samples and showed satisfactory performances.

Complexes of Th(IV) with neutral O-N-N-O hybrid ligands: a thermodynamic and crystallographic study.

The thermodynamics of Th(iv) complexes with N,N,N',N'-tetramethyl-2,2'-bipyridine-6,6'-dicarboxamide (TMBiPDA) and N,N,N',N'-tetramethyl-1,10-phenanthroline-2,9-dicarboxamide (TMPhenDA) in CH3OH/10%(v)H2O (CH3OH : H2O = 9 : 1 by volume) were determined by spectrophotometry and calorimetry. The ligand TMBiPDA/TMPhenDA coordinates with the central Th atom by the tetradentate (O-N-N-O) mode, which is validated by 1H NMR in solution and crystallography in the solid. The single crystal X-ray diffraction data show that ten-coordinated thorium coordinates with two ligand molecules and two solvent molecules (water or methanol). Both ThL and ThL2 complexes (L = TMPhenDA or TMBiPDA) were detected in solution. In thermodynamics, the formation of all complexes is driven by both enthalpy and entropy. In a comparison, enthalpy is more favorable to the formation of TMBiPDA complexes, while entropy is more favorable to the formation of TMPhenDA complexes; the entropy advantages of the TMPhenDA complexes override the enthalpy advantages of the corresponding TMBiPDA complexes, giving the TMPhenDA complexes higher stability constants than the TMBiPDA complexes. In crystallography, ligand distortions occur in ThL2 complexes, and TMBiDA distorts more than TMPhenDA does; the Th-O and Th-N bonds involving TMBiPDA are slightly shorter than those involving TMPhenDA.

Is skeletal muscle loss associated with chemoradiotherapy toxicity in nasopharyngeal carcinoma patients? A prospective study.

BACKGROUND: Our study explored to investigate whether skeletal muscle loss before concurrent chemoradiotherapy (CCRT) can predict treatment-related toxicity in this population. METHODS: Computed tomography (CT) scan of the third lumbar were used to assess and calculate the SMA (skeletal muscle area), SMI (skeletal muscle index), SMD (skeletal muscle density), SMG (skeletal muscle gauge) and estimate LBM (lean body mass). Handgrip strength (HGS) and daily walk speed were evaluated. Predictive factors linked to toxicity were assessed by logistic regression models and adjusted odds ratios (OR) of treatment toxicity were reported. RESULTS: A total of 82 patients were evaluated (67.1% males, 45.7 ± 10.7 years). Skeletal muscle loss was not associated with severe radiotherapy toxicity. In males, sarcopenia increases the risk of dose-limiting toxicity (DLT) (OR: 4.00, 95% CI = 1.20-13.36, p = 0.024). DLT is associated with reduced SMA (OR: 0.97, 95% CI = 0.94-1.00, p = 0.041), SMI (OR: 0.91, 95% CI = 0.84-0.99, p = 0.042) and LBM (OR: 0.90, 95% CI = 0.81-0.99, p = 0.041). Reduced HGS was significantly associated with grade 3-4 leukopenia (OR: 0.92, 95% CI = 0.86-0.98, p = 0.007), and was associated with any grade 3-4 toxicity (OR: 0.94, 95% CI = 0.89-0.99, p = 0.013). There is a strong correlation between LBM and HGS (Pearson's r = 0.71, p < 0.001). CONCLUSIONS: Skeletal muscle loss was not associated with severe radiation oral mucositis and dermatitis but associated with any grade 3-4 toxicity and severe gastrointestinal reactions in NPC patients. In males, sarcopenia before treatment is predictive of DLT. Increased HGS is independently associated with a reduced risk of hematological toxicity.

Effects of Infant Formula Supplemented With Prebiotics and OPO on Infancy Fecal Microbiota: A Pilot Randomized Clinical Trial.

Several lines of evidence suggest that the intestinal microbiota plays crucial roles in infant development, and that it is highly influenced by extrinsic and intrinsic factors. Prebiotic-containing infant formula may increase gastrointestinal tolerance and improve commensal microbiota composition. However, it remains unknown whether supplementation of milk-formulas with prebiotics and 1,3-olein-2-palmitin (OPO) can achieve feeding outcomes similar to those of breastfeeding. In the present study, we investigated the effects of two kinds of infant formula with different additives on the overall diversity and composition of the fecal microbiota, to determine which was closer to breastfeeding. A total of 108 infants were enrolled, including breastfeeding (n=59) and formula feeding group (n=49). The formula feeding infants were prospectively randomly divided into a standard formula group (n=18), and a supplemented formula group(n=31). The fecal samples were collected at 4 months after intervention. Fecal microbiota analysis targeting the V4 region of the 16S rRNA gene was performed using MiSeq sequencing. The overall bacterial diversity and composition, key functional bacteria, and predictive functional profiles in the two different formula groups were compared with breastfeeding group. We found that the alpha diversity of the gut microbiota was not significantly different between the OPO and breastfeeding groups with Chaos 1 index (p=0.346). The relative abundances of Enhydrobacter and Akkermansia in the OPO group were more similar to those of the breastfeeding group than to those of the standard formula group. The gut microbiota metabolism function prediction analysis showed that the supplemented formula group was similar to the breastfeeding group in terms of ureolysis (p=0.297). These findings suggest that, when formula supplemented with prebiotics and OPO was given, the overall bacterial diversity and parts of the composition of the fecal microbiota would be similar to that of breastfeeding infants.

Weighted gene co-expression network analysis identifies specific modules and hub genes related to Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. This study aims to screen specific modules and key genes related to PD. METHODS: Gene expression profile data GSE6613 and GSE22491 were downloaded from the Gene Expression Omnibus database. The significantly differentially expressed genes (DEGs) in different datasets were screened, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was used to screen disease-related modules that are significantly stable across datasets. The protein-protein interaction network was constructed using the DEGs in the stable module obtained and preservation modules. Finally, the hub genes directly related to PD were screened. RESULTS: A total of 179 DEGs with the same significant difference direction were screened. The enrichment analysis of GO and KEGG pathways showed that 20 significantly related GO biological processes and 9 KEGG signaling pathways were screened. A total of three highly conservative modules were detected in the WGCNA network. Finally, three significant PD-related KEGG pathways screened from the Comparative Toxicogenomics Database were identified, including neuroactive ligand-receptor interaction (CRHR2, CTSG, GRIN1, GRIN2D, LPAR4 and P2RX3), amyotrophic lateral sclerosis (BCL2, GRIN1 and GRIN2D) and alcoholism (CAMKK2, GRIN1, GRIN2D and SLC18A2). Key genes, such as SLC18A2, GRIN1 and GRIN2D, may be potential candidate genes for PD progression. CONCLUSIONS: Our findings indicate that SLC18A2, GRIN1 and GRIN2D may play an important role in the pathogenesis of PD.

Inhibition of latent transforming growth factor-beta1 activation by lentivirus-mediated short hairpin RNA targeting the CD36 gene in NR8383 cells.

CD36, a cell surface receptor for thrombospondin-1 (TSP-1), is believed to interact with latent transforming growth factor-beta1 (L-TGF-beta1) thereby activating its fibrogenic bioactivity. In this study, a lentiviral vector expressing a short hairpin RNA (shRNA) targeting the rat CD36 gene (Lv-shCD36) is developed and tested. To observe the inhibitory effect of Lv-shCD36 on the activation of L-TGF-beta1, a rat alveolar macrophage cell line (NR8383), infected with either Lv-shCD36 or Lv-shCD36-NC (non-silenced control lentivirus), was treated with 0.1 microg/ml bleomycin, which is known to stimulate alveolar macrophages to release increasing amounts of TGF-beta1. The results show that Lv-shCD36 can suppress expression of CD36 mRNA and protein in bleomycin-treated NR8383 cells. By quantifying active and total TGF-beta1 in the supernatant, it was discovered that the quantity of total TGF-beta1 is not significantly different between the three groups, while the quantity and percent of active TGF-beta1 in the Lv-shCD36 group was significantly lower than in either the bleomycin-treated group or the Lv-shCD36-NC group, respectively (P < 0.05). These results suggest that Lv-shCD36 can inhibit activation of L-TGF-beta1 secreted in bleomycin-treated NR8383 cells by decreasing the expression of CD36 on the cell membrane, thereby reducing binding of CD36 to TSP-1.

A CD36 synthetic peptide inhibits silica-induced lung fibrosis in the mice.

Silicosis is a kind of pneumoconiosis caused by inhalation of silica dust, which is characterized by lung fibrosis. The biologically active form of transforming growth factor-beta1 (TGF-beta1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF-beta1) to active TGF-beta1. The antagonistic effect of the synthetic peptide was analyzed by the administration of CD36 (93-110) synthetic peptide to the silicosis model of mice. The hydroxyproline content of the silica + CD36 (93-110) synthetic peptide group was significantly lower than that of the other experimental groups [silica and silica + CD36 (208-225) synthetic peptide groups] (p < .05). Inflammation, fibrotic degree and distribution of collagen fibers in silicotic nodules of the silica + CD36 (93-110) synthetic peptide group were less than those of the other experimental groups. The expressions of collagen I and III of the silica + CD36 (93-110) synthetic peptide group were significantly lower than those of the other experimental groups (p < .05). CD36 (93-110) synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the silicosis model of mice, resulting in the decreased severity of silica-induced lung fibrosis.

KAT6B Genetic Variant Identified in a Short Stature Chinese Infant: A Report of Physical Growth in Clinical Spectrum of KAT6B-Related Disorders.

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS, OMIM#603736) and genitopatellar syndrome (GTPTS, OMIM#606170), characterized by global developmental delay/intellectual disability and special clinical manifestations, are two distinct clinically overlapping syndromes caused by truncating sequence variants in the KAT6B (10q22.2) gene. We detected a de novo heterozygous variant within exon 16 of KAT6B (Chr10p: 76781966-76781967) in a 7-months-old female infant who showed symptoms of short stature, global developmental delay, blepharophimosis, and lacrimal duct anomalies highly consistent with SBBYSS. Following the clinical features, we analyzed the KAT6B gene using Next Generation Sequencing (NGS) techniques. Her parents didn't present the same genetic variant. The patient we reported here is mainly characterized by syndromic forms of short stature and developmental delay, which may contribute to the understanding of clinical genetics for KAT6B-associated disorders.

An electrochemical aptasensor-based CoxP-decorated porous carbon microspheres and AuNRs labelled methylene blue as signal labels for the sensitive detection of PCB77.

In this work, a simple, specific and ultra-sensitive electrochemical aptasensor was successfully developed based on a novel signal reduction strategy for the detection of polychlorinated biphenyls (PCB77). This aptasensor was prepared by the electrodeposition of gold nanoparticles (AuNPs) on an Au electrode (AuE) modified with cobalt phosphide (CoxP, a mixture of CoP and Co2P) decorated porous carbon microspheres. In this study, the thiolated single-complementary DNA (cDNA) was immobilized on the surface of the modified electrode via the Au-S bond. Subsequently, the gold nanorod@methylene blue connection aptamer (AuNRs@MB-Apt) signal labels were immobilized onto the modified electrode through the principle of complementary base pairing. Further, the aptamer preferentially binds to PCB77, decreasing the amount of AuNR@MB-Apt. The DPV current response was related to the PCB77 concentration. Under the optimized experimental conditions, a low detection limit of 5.9 × 10-2 ng L-1 and a wide linear range of 1 × 10-11 mg mL-1 to 1 × 10-4 mg mL-1 (S/N = 3) for PCB77 were achieved. Moreover, the proposed aptasensor offered high selectivity, stability and reproducibility, indicating the broad potential application in environmental monitoring.

Silencing CD36 gene expression results in the inhibition of latent-TGF-beta1 activation and suppression of silica-induced lung fibrosis in the rat.

BACKGROUND: The biologically active form of transforming growth factor-beta1 (TGF-beta1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF-beta1) to active TGF-beta1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-beta1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression. METHODS: The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-beta1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis. RESULTS: The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-beta1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups. CONCLUSION: These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-beta1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.

Silence of lncRNA GAS5 alleviates high glucose toxicity to human renal tubular epithelial HK-2 cells through regulation of miR-27a.

Renal tubular damage caused by persistent high glucose environment has been found to contribute to diabetic nephropathy. This study explored the effects of lncRNA growth arrest-specific 5 (GAS5) on high glucose-stimulated human renal tubular epithelial HK-2 damage, as well as the possible internal molecular mechanism. Viability and apoptosis of HK-2 cells were assessed with the help of CCK-8 assay and Annexin V-FITC/PI staining, respectively. Cell transfection was used to change the expression of GAS5, miR-27a and BNIP3. We found that high glucose stimulation suppressed HK-2 cell viability but induced cell apoptosis. The expression of GAS5 was increased in HK-2 cells under high glucose environment. Silence of GAS5 mitigated the high glucose-caused HK-2 cell viability reduction and apoptosis. Overexpression of miR-27a reversed the effects of GAS5 on high glucose-stimulated HK-2 cells. Overexpression of BNIP3 aggravated the high glucose-caused HK-2 cell viability reduction, apoptosis and activation of JNK pathway. Knockdown of BNIP3 had opposite effects. In conclusion, this research further confirmed the pro-apoptotic roles of GAS5 in renal tubular epithelial cells under high glucose environment. Silence of GAS5 alleviated high glucose toxicity to human renal tubular epithelial HK-2 cells might be via down-regulating miR-27a and BNIP3, and then inactivating JNK pathway. Highlights HG suppresses HK-2 cell viability, but promotes cell apoptosis; HG enhances the expression of GAS5 in HK-2 cells; Silence of GAS5 alleviates the HG-caused HK-2 cell toxicity; miR-27a participates in the effects of GAS5 silencing on HG-stimulated HK-2 cells; BNIP3 is regulated by miR-27a and related to the HG toxicity to HK-2 cells.

Arbutin protects HK-2 cells against high glucose-induced apoptosis and autophagy by up-regulating microRNA-27a.

Arbutin (ARB) has been widely used in skin pigmentation disorders. Nevertheless, the involvements of ARB in diabetic nephropathy (DN) are still unknown. We investigated the functions of ARB in high glucose (HG)-induced cell apoptosis and autophagy in HK-2 cells. Cell viability was examined through CCK-8 in HK-2 cells after disposal with 45 mM glucose and ARB (10-50 µM). Flow cytometry and western blot tested cell apoptosis and the related protein levels in HK-2 cells after 45 mM glucose and 50 µM ARB administration. RT-qPCR delved microRNA (miR)-27a expression in HG and ARB co-treated HK-2 cells. Effect of miR-27a on ARB affected cell apoptosis and autophagy was investigated after miR-27a inhibitor transfection. JNK and mTOR pathways were finally assessed by western blot. ARB alleviated HG-induced cell apoptosis, autophagy and regulated the related protein levels in HK-2 cells. MiR-27a expression was reduced in HG-treated cells, but was accelerated in HG and ARB co-treated HK-2 cells with the increased concentration. Inhibition of miR-27a apparently abolished the outcomes of ARB in HG-induced HK-2 cells apoptosis and autophagy. Besides, ARB blocked JNK and mTOR pathways by regulating miR-27a. The findings demonstrated that ARB alleviated apoptosis and autophagy in HG-treated HK-2 cells by regulating miR-27a/JNK/mTOR axis.