N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

Erectile Dysfunction in Type-2 Diabetes Mellitus Patients: Predictors of Early Detection and Treatment.

PURPOSE: To identify risk factors and potential predictors of erectile dysfunction (ED) in type-2 diabetes mellitus (T2DM) patients for early detection and treatment. METHODS: A retrospective cohort was used to assess the clinical data of 105 diabetic patients with ED from May 2019 to April 2020 age-matched to 105 diabetic patients without ED. Potential risk factors that could contribute to ED were compared between the groups. Erectile function was evaluated using the International Index of Erectile Function-5 questionnaire. RESULTS: There were higher rates of diabetic peripheral neuropathy (p = 0.036) and retinopathy (p < 0.001), longer duration of diabetes (p < 0.001), lower estimated glomerular filtration rate (p = 0.010) values, and higher uric acid (p < 0.001) and C-reactive protein (p = 0.001) levels in the ED group compared to the non-ED group. Multivariate logistic analysis identified uric acid, diabetic retinopathy, and T2DM course as independent predictors of diabetic ED. Diabetics with retinopathy and T2DM for ≥49 months were 3.028 and 3.860 times more likely to have ED, respectively. Uric acid values ≥392.5 µmol/L were associated with 18.638 times greater risk of having ED, though the values were within normal range. CONCLUSION: In T2DM patients, higher uric acid (≥392.5 µmol/L), longer diabetes duration (≥49 months), and the presence of diabetic retinopathy were important and reliable predictors for diabetic ED. For patients who have high risk factors for developing ED, diligent screening and early treatment are necessary.

Corrigendum to "Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia".

[This corrects the article DOI: 10.1155/2020/7286958.].

Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia.

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine É£-lyase (CSE) and cystathionine ß-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.

Synthesis and in vitro sorption properties of PAA-grafted cellulose beads for selective binding of LDL.

Poly(acrylic acid) (PAA)-grafted cellulose copolymer beads were synthesized and tested in vitro as an adsorbent for selective removal of low-density lipoprotein (LDL) from human plasma. The copolymers were prepared by graft copolymerization of acrylic acid (AA) onto porous cellulose beads using cerium ammonium nitrate (CAN) as an initiator. The effect of initiator concentration, monomer amount and reaction time on the grafting was examined, and it revealed that the extent of grafting could be controlled by setting the appropriate reaction conditions. In vitro batch-wise adsorption tests were conducted to evaluate the lipoprotein sorption properties of the resulted copolymer beads, and the effect of grafting conditions on the adsorption performance was investigated. It was shown that the binding capacities of the best adsorbent derived from the appropriate reaction conditions could reach 4.96 mg/g total cholesterol (TC) and 4.46 mg/g LDL cholesterol (LDL-C) from human plasma, respectively, without significantly affecting the contents of beneficial constitutes such as high-density lipoprotein (HDL) and total proteins (TP). The influences of plasma amount and adsorption period on the adsorption properties were also determined and analyzed. It appears that this kind of copolymer is worthy of being developed as an alternative LDL adsorbent.

Double-responsive polymer brushes on the surface of colloid particles.

Well-defined poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes were synthesized on the surface of polystyrene latex particles by atom transfer radical polymerization (ATRP). It was found that the surface-initiated polymerization of DMAEMA catalyzed by CuCl/CuCl(2)/bpy was under good control in the solvent of acetone/water at ambient temperature (35 degrees C). High-density PDMAEMA brushes with low polydispersity (PDI 1.21) were obtained. TEM results demonstrate that the PDMAEMA-grafted particles have core-shell structure. Dynamic light scattering studies indicate that the particles with PDMAEMA brushes are both pH and temperature responsive.

Adsorption mechanism at the molecular level between polymers and uremic octapeptide by the 2D 1H NMR Technique.

To remove uremic octapeptide from the blood stream of uremic patients, various modified polyacylamide cross-linked absorbents were prepared. Adsorption experiments showed these absorbents have significant differences in adsorption capacity to the target peptide. In this paper, two-dimension proton nuclear magnetic resonance (2D 1H NMR) spectroscopy was used to investigate the interaction mechanism between the peptide and the adsorbents. Because of the insolubility of the absorbent, some soluble linear polymers with the same functional groups as the absorbents were employed as the model adsorbents in 2D 1H NMR. The preferred binding site for the peptide and polymers was identified to be at the C-terminal carboxyl group of the octapeptide via chemical shift perturbation effects. In this study, we found that hydrogen bonding, electrostatic, and hydrophobic interactions all play a role in the interaction force but had different contributions. Especially, the great chemical shift changes of the aromatic amino acid residues (Trp) during the interaction between butyl-modified polyacrylamide and octapeptide suggested the hydrophobic interaction, incorporated with the electrostatic force, played an important role in the binding reaction in aqueous solutions. This information not only rationally explained the results of the adsorption experiments, but also identified the effective binding site and mechanism, and shall provide a structural basis for designing better affinity-type adsorbents for the target peptide.

Soft vesicles formed by diblock codendrimers of poly(benzyl ether) and poly(methallyl dichloride).

The synthesis of a block codendrimer (g3-PBE-b-g3-PMDC), composed of a third-generation poly(benzyl ether) (PBE) monodendron and an aliphatic polyether (PMDC) monodendron is reported. In THF/diiospropyl ether (1:1) the PMDC block functions as a "hydrophilic" block, while the PBE acts as a "hydrophobic" block. The codendrimer can form interdigitated layers leading to vesicle formation. Tapping mode atomic force microscopy (AFM), dynamic light scattering (DLS), and transmission electron microscopy (TEM) were used to characterize the vesicles. The effect of molecular architecture on the formation of the interdigitated layers and vesicles was studied.

Chitosan adsorbents carrying amino acids for selective removal of low density lipoprotein.

Chitosan beads carrying various amino acids (a total of 12 kinds) were synthesized through quite simple procedures for selective removal of low density lipoprotein (LDL). Macroporous chitosan beads were prepared by the phase-inversion method, to which the amino acids were then coupled respectively, via either ethyleneglycol diglycidylether (EGDE) or epichlorohydrin (ECH). Among the amino acids used, in vitro tests proved L-Trp to be the best ligand for binding LDL. The adsorbent, which was prepared by coupling L-Trp to the chitosan beads via EGDE, demonstrated satisfactory adsorption performance for selective removal of LDL in human plasma.

Isotherm analysis of phenol adsorption on polymeric adsorbents from nonaqueous solution.

Macroporous poly(methyl methacrylate-co-divinylbenzene) (PMMA), interpenetrating polymer adsorbent based on poly(styrene-co-divinylbenzene) (PS) and poly(methyl methacrylate-co-divinylbenzene) (PMMA/PS), and macroporous cross-linked poly(N-p-vinylbenzyl acetylamide) (PVBA) were prepared for the adsorption of phenol from cyclohexane. The sorption isotherms of phenol on the three polymeric adsorbents were measured and fitted to Langmuir and Freundlich isotherms. It is shown that the Langmuir isotherm, which is based on a homogeneous surface model, is unsuitable to describe the sorption of phenol on the adsorbents from nonaqueous solution and the Freundlich equation fits the tested three adsorption systems well. The isosteric enthalpy was quantitatively correlated with the fractional loading for the sorption of phenol onto the three polymeric adsorbents. The surface energetic heterogeneity patterns of the adsorbents were described with functions of isosteric enthalpy. The results showed that the tested three polymeric adsorbents exhibited different surface energetic heterogeneity patterns. The initial isosteric enthalpy of phenol sorption on polymeric adsorbent has to do with the surface chemical composition and is free from the pore structure of the polymeric adsorbent matrix. Forming hydrogen bonds between phenol molecules and adsorbent is the main driving force of phenol sorption onto PVBA and PMMA adsorbent from nonaqueous solution. When phenol is adsorbed on PMMA/PS, pi-pi interaction resulting from the stacking of the benzene rings of the adsorbed phenol molecules and the pendant benzene ring of adsorbent is involved.

Formation of spindlelike aggregates and flowerlike arrays of polystyrene-b-poly(acrylic acid) micelles.

In this letter we describe a simple physical method for the ordered aggregation of scattered single spherical polystyrene-b-poly(acrylic acid) (PS-b-PAA) micelles. First, narrow dispersed spindlelike aggregates, about 60 nm in diameter and 1.5 microm in length, are obtained from the aggregation of single spherical PS-b-PAA micelles at 0 degrees C on a glass slide. Then, the yielding spindlelike units can further aggregate into long-ranged, close-packed, flowerlike arrays after a given amount of freeze-thaw cycles. The formation of the interesting arrays is ascribed to the templated aggregation of micelles on the water polycrystal at the freezing point.

Individual substitution analogs of Mel(12-26), melittin's C-terminal 15-residue peptide: their antimicrobial and hemolytic actions.

Residues 1-9 of M(12-26) (GLPALISWIKRKRQQ-NH2), the C-terminal 15-residue segment of melittin, were substituted individually to change the hydropathicities in these positions. Antimicrobial and hemolytic activities of these peptides were determined. The results showed increased antimicrobial activities with increased hydrophobicities at almost all the positions studied. The effects at positions 2, 5, 8 and 9 were significant while the effects at the other positions were small. These two groups of residues were located on the opposite faces of the alpha-helix. In other words, the hydrophobicities of the two faces were favorable, but one face (the more favorable face) contributed more to the antimicrobial activities than the other (the less favorable face). The hydrophobicity, not the amphipathicity, seems to be crucial for antimicrobial activity. In contrast, the hydrophobicity of one face was favorable but the other was unfavorable for the hemolytic activity, indicating that the amphipathicity may be important for hemolysis. Interestingly, the more favorable face for antimicrobial activity was located opposite to the favorable face for hemolytic activity, indicating the direction of the hydrophobic face for the antimicrobial activity and direction of the amphipathicity for the hemolytic activity were also important.

[Studies on the toxic effects of magnetic targeting adriamycin-carboxymethyldextran magnetic nanoparticles].

In this paper, adriamycin-carboxymethyldextran magnetic nanoparticles (ADR-CMD MNPs) were prepared. After i.v. administration in mice, acute toxicity, cumulative toxicity and the distribution profiles of heart were studied both for free adriamycin(ADR) and ADR-CMD MNPs. The results showed conjugation with CMD MNPs, the acute toxicity of ADR was decreased significantly, the LD50 value of ADR-CMD MNPs was 5.06 times as high as that of the free ADR. Altogether, the cumulative toxicity of conjugate MNPs is significantly decreased as expressed by the mortality, the loss for both weight and leucocyte after repeated injection. Tissue distribution studies show the reduced cardiac uptake of ADR after i.v. which possibly contributes to minimizing the cardiotoxic effect of ADR.

Bone repair in radii and tibias of rabbits with phosphorylated chitosan reinforced calcium phosphate cements.

Biocompatibility of two calcium phosphate cements (CPCs), reinforced with phosphorylated chitosan (P-chitosan), was investigated in rabbits in present study. The two CPCs are monocalcium phosphate monohydrate (MPCM) with calcium oxide (CaO) in 1 M phosphate buffer (i.e. MCPM/CaO/1 M phosphate buffer cement, CPC-I) and dicalcium phosphate dihydrate (DCPD) with calcium hydroxide [Ca(OH)2] in 1 M Na2HPO4 solution (i.e. DCPD/Ca(OH)2/1 M Na2HPO4 cement, CPC-II). Different amount of P-chitosan was added to the liquid phase before the power phase was mixed with the liquid phase. The MCPM/CaO/1 M phosphate buffer/P-chitosan cements (P-CPC-I) with neutral pH were filled into the holey defects of rabbit tibias. While the DCPD/Ca(OH)2/1 M Na2HPO4/P-chitosan cements (P-CPC-II) shaped as prehardened cylinders were implanted into rabbit radial defects. After operation, the two serial groups and CPC-II controls were observed for 1, 4, 12 and 22 weeks, respectively. Histological and histomorphological studies proved that P-chitosan containing cements are biocompatible, bioabsorbable and osteoinductive. The biodegradation rate has a negative relationship with the P-chitosan content. Progressive substitution took place at the interface of implants and host bones. No adverse effects were found in tissues around the bone defects. Thus, they could be used as bone substitutes in clinic.

Utilization of synergetic effect of weak interactions in the design of polymeric sorbents with high sorption selectivity.

Cystine and tyrosine were used as model sorbates to illustrate the design of sorbents with high sorption selectivity using two types of weak interactions that act synergistically. When two types of weak interactions are the driving forces in a sorption and they act synergistically, the second interaction would be effectively intramolecular. The entropy lost for the second interaction should be lower than that for the same interaction that occurs alone, and thus a significant enhancement of sorption should result. We designed an N-acetyl aminomethyl polystyrene resin (N-acetyl HC-D309), which was expected to sorb tyrosine through hydrophobic interaction and hydrogen bonding but not cystine. The chromatographic results for tyrosine and cystine indicate that the separation efficiencies on the N-acetyl HC-D309 column are higher than those on a styrene-divinylbenzene copolymer column, on which sorption should be driven by hydrophobic interaction only, and on an acrylamide-N,N'-methylene bisacrylamide copolymer column, on which sorption should be driven by hydrogen bonding only. Tyrosine as well as cystine had no retention at all on the acrylamide-N,N'-methylene bisacrylamide copolymer column. indicating the hydrogen bonding had little contribution to the sorption when it acted alone. The above results further indicate that hydrophobic interaction and hydrogen bonding contributed to the sorption of tyrosine on N-acetyl HC-D309 and they also acted synergistically. One of the conclusions of this paper is that some weak interactions which contribute little to the sorption when they act alone may contribute to the sorption when they act synergistically with other interactions.